Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)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: 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

BioCyciZFISH:ENSG00000106927-MONOMER.
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

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...)1 Publication1
Glycosylationi36N-linked (GlcNAc...) (complex)1 Publication1
Disulfide bondi91 ↔ 188
Glycosylationi115N-linked (GlcNAc...) (complex)2 Publications1
Glycosylationi215O-linked (Xyl...) (chondroitin sulfate)3 Publications1
Disulfide bondi231 ↔ 281
Disulfide bondi240 ↔ 264
Glycosylationi250N-linked (GlcNAc...) (complex)2 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

Proteomic databases

MaxQBiP02760.
PaxDbiP02760.
PeptideAtlasiP02760.
PRIDEiP02760.

2D gel databases

SWISS-2DPAGEP02760.

PTM databases

iPTMnetiP02760.
PhosphoSitePlusiP02760.
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 interactors.
IntActiP02760. 11 interactors.
MINTiMINT-1367019.
STRINGi9606.ENSP00000265132.

Structurei

Secondary structure

1352
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi37 – 39Combined sources3
Beta strandi42 – 51Combined sources10
Helixi54 – 59Combined sources6
Helixi60 – 62Combined sources3
Beta strandi66 – 72Combined sources7
Beta strandi78 – 87Combined sources10
Beta strandi90 – 100Combined sources11
Beta strandi106 – 111Combined sources6
Turni112 – 115Combined sources4
Beta strandi116 – 125Combined sources10
Beta strandi127 – 142Combined sources16
Beta strandi145 – 155Combined sources11
Helixi159 – 170Combined sources12
Turni171 – 173Combined sources3
Helixi176 – 178Combined sources3
Beta strandi179 – 181Combined sources3
Beta strandi244 – 250Combined sources7
Turni251 – 254Combined sources4
Beta strandi255 – 261Combined sources7
Beta strandi263 – 265Combined sources3
Beta strandi271 – 273Combined sources3
Helixi274 – 281Combined sources8
Helixi284 – 288Combined sources5
Beta strandi300 – 306Combined sources7
Turni307 – 310Combined sources4
Beta strandi311 – 317Combined sources7
Beta strandi319 – 321Combined sources3
Beta strandi327 – 329Combined sources3
Helixi330 – 337Combined sources8

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[»]
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
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)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. 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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BIKX-ray2.50A206-352[»]
3QKGX-ray2.30A20-202[»]
4ES7X-ray2.00A27-193[»]
4U30X-ray2.50W/X/Y/Z283-340[»]
ProteinModelPortaliP02760.
SMRiP02760.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

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

Protein family/group databases

MEROPSiI02.005.

PTM databases

iPTMnetiP02760.
PhosphoSitePlusiP02760.
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.
DisGeNETi259.
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

BioCyciZFISH:ENSG00000106927-MONOMER.
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: November 2, 2016
This is version 198 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.