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Protein

Protein AMBP

Gene

AMBP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei53Multimeric 3-hydroxykynurenine chromophore (covalent)1
Binding sitei111Multimeric 3-hydroxykynurenine chromophore (covalent)1
Binding sitei137Multimeric 3-hydroxykynurenine chromophore (covalent)1
Binding sitei149Multimeric 3-hydroxykynurenine chromophore (covalent)1
Sitei241 – 242Inhibitory (P1) (chymotrypsin, elastase)By similarity2
Sitei297 – 298Inhibitory (P1) (trypsin)By similarity2

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: GO_Central

GO - Biological processi

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor
Biological processHost-virus interaction
LigandChromophore

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

EuPathDBiHostDB:ENSG00000106927.11
HGNCiHGNC:453 AMBP
MIMi176870 gene
neXtProtiNX_P02760

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi259
OpenTargetsiENSG00000106927
PharmGKBiPA24759

Chemistry databases

DrugBankiDB00062 Human Serum Albumin
DB00064 Serum albumin iodonated

Polymorphism and mutation databases

BioMutaiAMBP
DMDMi122801

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 193 PublicationsAdd BLAST19
ChainiPRO_000001788620 – 203Alpha-1-microglobulinAdd BLAST184
ChainiPRO_0000017887206 – 352Inter-alpha-trypsin inhibitor light chainAdd BLAST147
ChainiPRO_0000318926284 – 344TrypstatinBy similarityAdd BLAST61

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
GlycosylationiCAR_00017224O-linked (GalNAc...) threonine1 Publication1
Glycosylationi36N-linked (GlcNAc...) (complex) asparagine1 Publication1
Disulfide bondi91 ↔ 188
Glycosylationi115N-linked (GlcNAc...) (complex) asparagine2 Publications1
Glycosylationi215O-linked (Xyl...) (chondroitin sulfate) serine3 Publications1
Disulfide bondi231 ↔ 281
Disulfide bondi240 ↔ 264
Glycosylationi250N-linked (GlcNAc...) (complex) asparagine2 Publications1
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, Proteoglycan

Proteomic databases

MaxQBiP02760
PaxDbiP02760
PeptideAtlasiP02760
PRIDEiP02760
ProteomicsDBi51583

2D gel databases

SWISS-2DPAGEiP02760

PTM databases

CarbonylDBiP02760
GlyConnecti1650
21
iPTMnetiP02760
PhosphoSitePlusiP02760
UniCarbKBiP02760

Miscellaneous databases

PMAP-CutDBiP02760

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 Expressed in 93 organ(s), highest expression level in liver
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).By similarity
(Microbial infection) Alpha-1-microglobulin and bikunin interact (via SH3 domain) with hepatitis E virus/HEV protein ORF3.2 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106757, 13 interactors
IntActiP02760, 12 interactors
MINTiP02760
STRINGi9606.ENSP00000265132

Structurei

Secondary structure

1352
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP02760
SMRiP02760
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02760

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini231 – 281BPTI/Kunitz inhibitor 1PROSITE-ProRule annotationAdd BLAST51
Domaini287 – 337BPTI/Kunitz inhibitor 2PROSITE-ProRule annotationAdd BLAST51

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni206 – 226Glycopeptide (secretory piece)Add BLAST21

Sequence similaritiesi

In the N-terminal section; belongs to the calycin superfamily. Lipocalin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG4295 Eukaryota
ENOG410XQNP LUCA
GeneTreeiENSGT00740000114929
HOVERGENiHBG000225
InParanoidiP02760
OrthoDBiEOG091G09P2
PhylomeDBiP02760
TreeFamiTF351222

Family and domain databases

CDDicd00109 KU, 2 hits
Gene3Di2.40.128.20, 1 hit
4.10.410.10, 1 hit
InterProiView protein in InterPro
IPR002968 A1-microglobln
IPR029856 AMBP
IPR012674 Calycin
IPR002223 Kunitz_BPTI
IPR036880 Kunitz_BPTI_sf
IPR022272 Lipocalin_CS
IPR000566 Lipocln_cytosolic_FA-bd_dom
IPR020901 Prtase_inh_Kunz-CS
PANTHERiPTHR10083:SF18 PTHR10083:SF18, 1 hit
PfamiView protein in Pfam
PF00014 Kunitz_BPTI, 2 hits
PF00061 Lipocalin, 1 hit
PRINTSiPR01215 A1MCGLOBULIN
PR00759 BASICPTASE
SMARTiView protein in SMART
SM00131 KU, 2 hits
SUPFAMiSSF50814 SSF50814, 1 hit
SSF57362 SSF57362, 2 hits
PROSITEiView protein in PROSITE
PS00280 BPTI_KUNITZ_1, 2 hits
PS50279 BPTI_KUNITZ_2, 2 hits
PS00213 LIPOCALIN, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
S4R3Y4S4R3Y4_HUMAN
Protein AMBP
AMBP
238Annotation score:
S4R471S4R471_HUMAN
Protein AMBP
AMBP
193Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48 – 57Missing AA sequence (PubMed:6164372).Curated10
Sequence conflicti57Missing AA sequence (PubMed:6198962).Curated1
Sequence conflicti57Missing AA sequence (Ref. 12) Curated1
Sequence conflicti137Missing AA sequence (PubMed:6164372).Curated1
Sequence conflicti142H → T AA sequence (PubMed:6164372).Curated1
Sequence conflicti145Missing AA sequence (PubMed:6164372).Curated1
Sequence conflicti194E → Q AA sequence (PubMed:6164372).Curated1
Sequence conflicti215S → T AA sequence (PubMed:7676539).Curated1
Sequence conflicti218G → T AA sequence (PubMed:7676539).Curated1
Sequence conflicti291 – 292IV → VI AA sequence (PubMed:2408638).Curated2
Sequence conflicti291 – 292IV → VI AA sequence (PubMed:1469060).Curated2
Sequence conflicti295Missing AA sequence (PubMed:1469060).Curated1
Sequence conflicti343G → E AA sequence (PubMed:2408638).Curated1

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 No translation available.
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
KEGGihsa:259
UCSCiuc004bie.5 human

Similar proteinsi

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 No translation available.
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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BIKX-ray2.50A206-352[»]
3QKGX-ray2.30A20-202[»]
4ES7X-ray2.00A27-193[»]
4U30X-ray2.50W/X/Y/Z283-340[»]
6EJ7X-ray2.00B210-221[»]
6EJ8X-ray2.09B210-221[»]
6EJ9X-ray2.02B210-220[»]
6EJAX-ray1.94B210-221[»]
6EJBX-ray2.56B210-221[»]
6EJCX-ray2.06B210-221[»]
6EJDX-ray2.68B210-221[»]
ProteinModelPortaliP02760
SMRiP02760
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106757, 13 interactors
IntActiP02760, 12 interactors
MINTiP02760
STRINGi9606.ENSP00000265132

Chemistry databases

DrugBankiDB00062 Human Serum Albumin
DB00064 Serum albumin iodonated

Protein family/group databases

MEROPSiI02.005

PTM databases

CarbonylDBiP02760
GlyConnecti1650
21
iPTMnetiP02760
PhosphoSitePlusiP02760
UniCarbKBiP02760

Polymorphism and mutation databases

BioMutaiAMBP
DMDMi122801

2D gel databases

SWISS-2DPAGEiP02760

Proteomic databases

MaxQBiP02760
PaxDbiP02760
PeptideAtlasiP02760
PRIDEiP02760
ProteomicsDBi51583

Protocols and materials databases

DNASUi259
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265132; ENSP00000265132; ENSG00000106927
GeneIDi259
KEGGihsa:259
UCSCiuc004bie.5 human

Organism-specific databases

CTDi259
DisGeNETi259
EuPathDBiHostDB:ENSG00000106927.11
GeneCardsiAMBP
HGNCiHGNC:453 AMBP
HPAiCAB069436
HPA001497
MIMi176870 gene
neXtProtiNX_P02760
OpenTargetsiENSG00000106927
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

ChiTaRSiAMBP human
EvolutionaryTraceiP02760
GeneWikiiAlpha-1-microglobulin/bikunin_precursor
GenomeRNAii259
PMAP-CutDBiP02760
PROiPR:P02760
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106927 Expressed in 93 organ(s), highest expression level in liver
CleanExiHS_AMBP
ExpressionAtlasiP02760 baseline and differential
GenevisibleiP02760 HS

Family and domain databases

CDDicd00109 KU, 2 hits
Gene3Di2.40.128.20, 1 hit
4.10.410.10, 1 hit
InterProiView protein in InterPro
IPR002968 A1-microglobln
IPR029856 AMBP
IPR012674 Calycin
IPR002223 Kunitz_BPTI
IPR036880 Kunitz_BPTI_sf
IPR022272 Lipocalin_CS
IPR000566 Lipocln_cytosolic_FA-bd_dom
IPR020901 Prtase_inh_Kunz-CS
PANTHERiPTHR10083:SF18 PTHR10083:SF18, 1 hit
PfamiView protein in Pfam
PF00014 Kunitz_BPTI, 2 hits
PF00061 Lipocalin, 1 hit
PRINTSiPR01215 A1MCGLOBULIN
PR00759 BASICPTASE
SMARTiView protein in SMART
SM00131 KU, 2 hits
SUPFAMiSSF50814 SSF50814, 1 hit
SSF57362 SSF57362, 2 hits
PROSITEiView protein in PROSITE
PS00280 BPTI_KUNITZ_1, 2 hits
PS50279 BPTI_KUNITZ_2, 2 hits
PS00213 LIPOCALIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAMBP_HUMAN
AccessioniPrimary (citable) accession number: P02760
Secondary accession number(s): P00977
, P02759, P78491, Q2TU33, Q5TBD7, Q9UC58, Q9UDI8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: November 7, 2018
This is version 217 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
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