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Protein

Haptoglobin

Gene

HP

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

Functioni

As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.1 Publication
Uncleaved haptoglogin, also known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.1 Publication

GO - Molecular functioni

  • antioxidant activity Source: UniProtKB-KW
  • hemoglobin binding Source: BHF-UCL

GO - Biological processi

  • acute-phase response Source: UniProtKB-KW
  • defense response Source: ProtInc
  • defense response to bacterium Source: UniProtKB-KW
  • immune system process Source: UniProtKB-KW
  • negative regulation of hydrogen peroxide catabolic process Source: BHF-UCL
  • negative regulation of oxidoreductase activity Source: BHF-UCL
  • positive regulation of cell death Source: BHF-UCL
  • receptor-mediated endocytosis Source: Reactome
  • response to hydrogen peroxide Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Antibiotic, Antimicrobial, Antioxidant, Serine protease homolog

Keywords - Biological processi

Acute phase, Immunity

Keywords - Ligandi

Hemoglobin-binding

Enzyme and pathway databases

BioCyciZFISH:G66-33890-MONOMER.
ReactomeiR-HSA-2168880. Scavenging of heme from plasma.
R-HSA-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiS01.972.

Names & Taxonomyi

Protein namesi
Recommended name:
Haptoglobin
Alternative name(s):
Zonulin
Cleaved into the following 2 chains:
Gene namesi
Name:HP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:5141. HP.

Subcellular locationi

GO - Cellular componenti

  • blood microparticle Source: UniProtKB
  • endocytic vesicle lumen Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: UniProtKB
  • haptoglobin-hemoglobin complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Anhaptoglobinemia (AHP)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by the absence of the serum glycoprotein haptoglobin. Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin. Congenital haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic transfusion reactions.
See also OMIM:614081
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_066214247I → T in AHP; causes reduced expression of the protein. 1 PublicationCorresponds to variant rs104894517dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3240.
MalaCardsiHP.
MIMi614081. phenotype.
OpenTargetsiENSG00000257017.
PharmGKBiPA29415.

Polymorphism and mutation databases

BioMutaiHP.
DMDMi123508.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 181 PublicationAdd BLAST18
ChainiPRO_000002845619 – 406HaptoglobinAdd BLAST388
ChainiPRO_000002845719 – 160Haptoglobin alpha chainAdd BLAST142
ChainiPRO_0000028458162 – 406Haptoglobin beta chainAdd BLAST245

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33Interchain
Disulfide bondi52 ↔ 86
Disulfide bondi92Interchain
Disulfide bondi111 ↔ 145
Disulfide bondi149 ↔ 266Interchain (between alpha and beta chains)
Glycosylationi184N-linked (GlcNAc...) (complex)4 Publications1
Glycosylationi207N-linked (GlcNAc...)5 Publications1
Glycosylationi211N-linked (GlcNAc...)4 Publications1
Glycosylationi241N-linked (GlcNAc...) (complex)6 Publications1
Disulfide bondi309 ↔ 340
Disulfide bondi351 ↔ 381

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP00738.
PaxDbiP00738.
PeptideAtlasiP00738.
PRIDEiP00738.

2D gel databases

DOSAC-COBS-2DPAGEP00738.
SWISS-2DPAGEP00738.

PTM databases

iPTMnetiP00738.
PhosphoSitePlusiP00738.
SwissPalmiP00738.
UniCarbKBiP00738.

Expressioni

Tissue specificityi

Expressed by the liver and secreted in plasma.

Gene expression databases

BgeeiENSG00000257017.
CleanExiHS_HP.
ExpressionAtlasiP00738. baseline and differential.
GenevisibleiP00738. HS.

Organism-specific databases

HPAiCAB003787.
HPA047750.

Interactioni

Subunit structurei

Tetramer of two alpha and two beta chains; disufide-linked. The Hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers. Interacts with CD163.

Binary interactionsi

WithEntry#Exp.IntActNotes
APOA1P026473EBI-1220767,EBI-701692
APOEP026497EBI-1220767,EBI-1222467

Protein-protein interaction databases

BioGridi109480. 25 interactors.
IntActiP00738. 18 interactors.
STRINGi9606.ENSP00000348170.

Structurei

Secondary structure

1406
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi101 – 111Combined sources11
Beta strandi115 – 121Combined sources7
Beta strandi123 – 127Combined sources5
Beta strandi133 – 135Combined sources3
Turni136 – 138Combined sources3
Beta strandi144 – 147Combined sources4
Beta strandi163 – 167Combined sources5
Beta strandi176 – 180Combined sources5
Beta strandi186 – 193Combined sources8
Beta strandi196 – 199Combined sources4
Helixi201 – 204Combined sources4
Turni205 – 207Combined sources3
Helixi214 – 217Combined sources4
Helixi218 – 220Combined sources3
Beta strandi222 – 225Combined sources4
Turni226 – 228Combined sources3
Beta strandi229 – 231Combined sources3
Beta strandi233 – 238Combined sources6
Turni240 – 244Combined sources5
Beta strandi248 – 254Combined sources7
Beta strandi259 – 261Combined sources3
Beta strandi278 – 283Combined sources6
Beta strandi290 – 292Combined sources3
Beta strandi297 – 303Combined sources7
Helixi306 – 314Combined sources9
Helixi319 – 321Combined sources3
Beta strandi327 – 330Combined sources4
Beta strandi338 – 341Combined sources4
Beta strandi358 – 363Combined sources6
Turni364 – 367Combined sources4
Beta strandi368 – 377Combined sources10
Turni381 – 383Combined sources3
Beta strandi387 – 391Combined sources5
Helixi392 – 394Combined sources3
Helixi396 – 405Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WJGX-ray3.102/C/H/M/R/W92-406[»]
4X0LX-ray2.05C148-406[»]
5HU6X-ray2.90C148-406[»]
ProteinModelPortaliP00738.
SMRiP00738.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 88Sushi 1PROSITE-ProRule annotationAdd BLAST58
Domaini90 – 147Sushi 2PROSITE-ProRule annotationAdd BLAST58
Domaini162 – 404Peptidase S1PROSITE-ProRule annotationAdd BLAST243

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni318 – 323Interaction with CD163By similarity6

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation
Contains 2 Sushi (CCP/SCR) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Sushi

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118890.
HOGENOMiHOG000112945.
HOVERGENiHBG005989.
InParanoidiP00738.
KOiK16142.
PhylomeDBiP00738.
TreeFamiTF334326.

Family and domain databases

CDDicd00033. CCP. 2 hits.
cd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP_dom.
IPR001254. Trypsin_dom.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEiPS50923. SUSHI. 2 hits.
PS50240. TRYPSIN_DOM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P00738-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSALGAVIAL LLWGQLFAVD SGNDVTDIAD DGCPKPPEIA HGYVEHSVRY
60 70 80 90 100
QCKNYYKLRT EGDGVYTLND KKQWINKAVG DKLPECEADD GCPKPPEIAH
110 120 130 140 150
GYVEHSVRYQ CKNYYKLRTE GDGVYTLNNE KQWINKAVGD KLPECEAVCG
160 170 180 190 200
KPKNPANPVQ RILGGHLDAK GSFPWQAKMV SHHNLTTGAT LINEQWLLTT
210 220 230 240 250
AKNLFLNHSE NATAKDIAPT LTLYVGKKQL VEIEKVVLHP NYSQVDIGLI
260 270 280 290 300
KLKQKVSVNE RVMPICLPSK DYAEVGRVGY VSGWGRNANF KFTDHLKYVM
310 320 330 340 350
LPVADQDQCI RHYEGSTVPE KKTPKSPVGV QPILNEHTFC AGMSKYQEDT
360 370 380 390 400
CYGDAGSAFA VHDLEEDTWY ATGILSFDKS CAVAEYGVYV KVTSIQDWVQ

KTIAEN
Length:406
Mass (Da):45,205
Last modified:July 21, 1986 - v1
Checksum:iA98B56B2B1BE891E
GO
Isoform 2 (identifier: P00738-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     38-96: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:347
Mass (Da):38,452
Checksum:i47EFE07D5FE15EB8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti70D → N in AAA52687 (PubMed:6310599).Curated1
Sequence conflicti130E → G in AAI07588 (PubMed:15489334).Curated1

Polymorphismi

In the human populations there are two major allelic forms, alpha-1 (1-1) with 83 residues and alpha-2 (2-2) with 142 residues. These alleles determine 3 possible genotypes, homozygous (1-1 or 2-2) and heterozygous (2-1), and 3 major phenotypes HP*1F/HP*1S and HP*2FS. The two main alleles of HP*1 are called HP*1F (fast) and HP*1S (slow). The alleles exhibit different oligomerization properties. In healthy males, but not in females, the Hp 2-2 phenotype is associated with higher serum iron, decreased Antimicrobial; Antioxidant capability, and less efficient clearance from the circulation, than Hp 1-1 and 2-1.3 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01711229 – 87Missing in allele HP*1F and allele HP*1S. 2 PublicationsAdd BLAST59
Natural variantiVAR_005294129N → D in allele HP*1F. 2 PublicationsCorresponds to variant rs199926732dbSNPEnsembl.1
Natural variantiVAR_017113130E → K in allele HP*1F. 1 PublicationCorresponds to variant rs200877317dbSNPEnsembl.1
Natural variantiVAR_066214247I → T in AHP; causes reduced expression of the protein. 1 PublicationCorresponds to variant rs104894517dbSNPEnsembl.1
Natural variantiVAR_017114397D → H.Corresponds to variant rs12646dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05502438 – 96Missing in isoform 2. CuratedAdd BLAST59

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K00422 mRNA. Translation: AAA52687.1.
K01763 mRNA. Translation: AAA52684.1.
L29394 mRNA. Translation: AAA52685.1.
X00637 mRNA. Translation: CAA25267.1.
X01793
, X01786, X02206, X01789, X01791 Genomic DNA. Translation: CAA25926.1.
M10935 Genomic DNA. Translation: AAA88080.1.
M69197 Genomic DNA. Translation: AAA88078.1.
AK314700 mRNA. Translation: BAF98793.1.
DQ314870 Genomic DNA. Translation: ABC40729.1.
AC004682 Genomic DNA. Translation: AAC27432.1.
AC009087 Genomic DNA. No translation available.
BC107587 mRNA. Translation: AAI07588.1.
BC121124 mRNA. Translation: AAI21125.1.
BC121125 mRNA. Translation: AAI21126.1.
M13192 mRNA. No translation available.
X00606 Genomic DNA. Translation: CAA25248.1.
CCDSiCCDS45524.1. [P00738-1]
CCDS45525.1. [P00738-2]
PIRiA92532. HPHU2.
A93521. HPHU1.
RefSeqiNP_001119574.1. NM_001126102.2. [P00738-2]
NP_001305067.1. NM_001318138.1.
NP_005134.1. NM_005143.4. [P00738-1]
UniGeneiHs.513711.
Hs.702099.

Genome annotation databases

EnsembliENST00000355906; ENSP00000348170; ENSG00000257017. [P00738-1]
ENST00000398131; ENSP00000381199; ENSG00000257017. [P00738-2]
ENST00000570083; ENSP00000457629; ENSG00000257017. [P00738-2]
GeneIDi3240.
KEGGihsa:3240.
UCSCiuc002fbr.5. human. [P00738-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Haptoglobin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K00422 mRNA. Translation: AAA52687.1.
K01763 mRNA. Translation: AAA52684.1.
L29394 mRNA. Translation: AAA52685.1.
X00637 mRNA. Translation: CAA25267.1.
X01793
, X01786, X02206, X01789, X01791 Genomic DNA. Translation: CAA25926.1.
M10935 Genomic DNA. Translation: AAA88080.1.
M69197 Genomic DNA. Translation: AAA88078.1.
AK314700 mRNA. Translation: BAF98793.1.
DQ314870 Genomic DNA. Translation: ABC40729.1.
AC004682 Genomic DNA. Translation: AAC27432.1.
AC009087 Genomic DNA. No translation available.
BC107587 mRNA. Translation: AAI07588.1.
BC121124 mRNA. Translation: AAI21125.1.
BC121125 mRNA. Translation: AAI21126.1.
M13192 mRNA. No translation available.
X00606 Genomic DNA. Translation: CAA25248.1.
CCDSiCCDS45524.1. [P00738-1]
CCDS45525.1. [P00738-2]
PIRiA92532. HPHU2.
A93521. HPHU1.
RefSeqiNP_001119574.1. NM_001126102.2. [P00738-2]
NP_001305067.1. NM_001318138.1.
NP_005134.1. NM_005143.4. [P00738-1]
UniGeneiHs.513711.
Hs.702099.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WJGX-ray3.102/C/H/M/R/W92-406[»]
4X0LX-ray2.05C148-406[»]
5HU6X-ray2.90C148-406[»]
ProteinModelPortaliP00738.
SMRiP00738.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109480. 25 interactors.
IntActiP00738. 18 interactors.
STRINGi9606.ENSP00000348170.

Protein family/group databases

MEROPSiS01.972.

PTM databases

iPTMnetiP00738.
PhosphoSitePlusiP00738.
SwissPalmiP00738.
UniCarbKBiP00738.

Polymorphism and mutation databases

BioMutaiHP.
DMDMi123508.

2D gel databases

DOSAC-COBS-2DPAGEP00738.
SWISS-2DPAGEP00738.

Proteomic databases

MaxQBiP00738.
PaxDbiP00738.
PeptideAtlasiP00738.
PRIDEiP00738.

Protocols and materials databases

DNASUi3240.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355906; ENSP00000348170; ENSG00000257017. [P00738-1]
ENST00000398131; ENSP00000381199; ENSG00000257017. [P00738-2]
ENST00000570083; ENSP00000457629; ENSG00000257017. [P00738-2]
GeneIDi3240.
KEGGihsa:3240.
UCSCiuc002fbr.5. human. [P00738-1]

Organism-specific databases

CTDi3240.
DisGeNETi3240.
GeneCardsiHP.
HGNCiHGNC:5141. HP.
HPAiCAB003787.
HPA047750.
MalaCardsiHP.
MIMi140100. gene.
614081. phenotype.
neXtProtiNX_P00738.
OpenTargetsiENSG00000257017.
PharmGKBiPA29415.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3627. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118890.
HOGENOMiHOG000112945.
HOVERGENiHBG005989.
InParanoidiP00738.
KOiK16142.
PhylomeDBiP00738.
TreeFamiTF334326.

Enzyme and pathway databases

BioCyciZFISH:G66-33890-MONOMER.
ReactomeiR-HSA-2168880. Scavenging of heme from plasma.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

GeneWikiiHaptoglobin.
GenomeRNAii3240.
PROiP00738.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000257017.
CleanExiHS_HP.
ExpressionAtlasiP00738. baseline and differential.
GenevisibleiP00738. HS.

Family and domain databases

CDDicd00033. CCP. 2 hits.
cd00190. Tryp_SPc. 1 hit.
InterProiIPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP_dom.
IPR001254. Trypsin_dom.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEiPS50923. SUSHI. 2 hits.
PS50240. TRYPSIN_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHPT_HUMAN
AccessioniPrimary (citable) accession number: P00738
Secondary accession number(s): B0AZL5
, P00737, Q0VAC4, Q0VAC5, Q2PP15, Q3B7J0, Q6LBY9, Q9UC67
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 189 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

Caution

Although homologous to serine proteases, it has lost all essential catalytic residues and has no enzymatic activity.Curated

Keywords - Technical termi

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

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.