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Protein

Haptoglobin

Gene

HP

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

Caution

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

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionAntibiotic, Antimicrobial, Antioxidant, Serine protease homolog
Biological processAcute phase, Immunity
LigandHemoglobin-binding

Enzyme and pathway databases

ReactomeiR-HSA-2168880 Scavenging of heme from plasma
R-HSA-6798695 Neutrophil degranulation
SIGNORiP00738

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

EuPathDBiHostDB:ENSG00000257017.8
HGNCiHGNC:5141 HP
MIMi140100 gene
neXtProtiNX_P00738

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

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 dbSNP:rs104894517EnsemblClinVar.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) asparagine4 Publications1
Glycosylationi207N-linked (GlcNAc...) asparagine5 Publications1
Glycosylationi211N-linked (GlcNAc...) asparagine4 Publications1
Glycosylationi241N-linked (GlcNAc...) (complex) asparagine6 Publications1
Disulfide bondi309 ↔ 340
Disulfide bondi351 ↔ 381

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP00738
MaxQBiP00738
PaxDbiP00738
PeptideAtlasiP00738
PRIDEiP00738
ProteomicsDBi51271

2D gel databases

DOSAC-COBS-2DPAGEiP00738
SWISS-2DPAGEiP00738

PTM databases

CarbonylDBiP00738
GlyConnecti744
iPTMnetiP00738
PhosphoSitePlusiP00738
SwissPalmiP00738
UniCarbKBiP00738

Expressioni

Tissue specificityi

Expressed by the liver and secreted in plasma.

Gene expression databases

BgeeiENSG00000257017 Expressed in 210 organ(s), highest expression level in liver
CleanExiHS_HP
ExpressionAtlasiP00738 baseline and differential
GenevisibleiP00738 HS

Organism-specific databases

HPAiCAB003787
HPA047750

Interactioni

Subunit structurei

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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109480, 27 interactors
IntActiP00738, 19 interactors
MINTiP00738
STRINGi9606.ENSP00000348170

Structurei

Secondary structure

1406
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
InterProiView protein in InterPro
IPR008292 Haptoglobin
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR035976 Sushi/SCR/CCP_sf
IPR000436 Sushi_SCR_CCP_dom
IPR001254 Trypsin_dom
PANTHERiPTHR44686 PTHR44686, 2 hits
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57535 SSF57535, 2 hits
PROSITEiView protein in PROSITE
PS50923 SUSHI, 2 hits
PS50240 TRYPSIN_DOM, 1 hit

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

This entry has 2 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DGL8A0A0C4DGL8_HUMAN
Haptoglobin
HP
347Annotation score:
J3QLC9J3QLC9_HUMAN
Haptoglobin
HP
365Annotation score:
H0Y300H0Y300_HUMAN
Haptoglobin
HP
442Annotation score:
H3BS21H3BS21_HUMAN
Haptoglobin
HP
222Annotation score:
J3QR68J3QR68_HUMAN
Haptoglobin
HP
404Annotation score:
H3BMJ7H3BMJ7_HUMAN
Haptoglobin
HP
92Annotation score:
J3KRH2J3KRH2_HUMAN
Haptoglobin
HP
149Annotation score:
J3KSV1J3KSV1_HUMAN
Haptoglobin
HP
88Annotation score:
J3QQI8J3QQI8_HUMAN
Haptoglobin
HP
91Annotation score:
A0A087WU08A0A087WU08_HUMAN
Haptoglobin
HP
281Annotation score:

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 dbSNP:rs199926732Ensembl.1
Natural variantiVAR_017113130E → K in allele HP*1F. 1 PublicationCorresponds to variant dbSNP:rs200877317Ensembl.1
Natural variantiVAR_066214247I → T in AHP; causes reduced expression of the protein. 1 PublicationCorresponds to variant dbSNP:rs104894517EnsemblClinVar.1
Natural variantiVAR_017114397D → H. Corresponds to variant dbSNP:rs189115161Ensembl.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.530274
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

Similar proteinsi

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.530274
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, 27 interactors
IntActiP00738, 19 interactors
MINTiP00738
STRINGi9606.ENSP00000348170

Protein family/group databases

MEROPSiS01.972

PTM databases

CarbonylDBiP00738
GlyConnecti744
iPTMnetiP00738
PhosphoSitePlusiP00738
SwissPalmiP00738
UniCarbKBiP00738

Polymorphism and mutation databases

BioMutaiHP
DMDMi123508

2D gel databases

DOSAC-COBS-2DPAGEiP00738
SWISS-2DPAGEiP00738

Proteomic databases

EPDiP00738
MaxQBiP00738
PaxDbiP00738
PeptideAtlasiP00738
PRIDEiP00738
ProteomicsDBi51271

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
EuPathDBiHostDB:ENSG00000257017.8
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

ReactomeiR-HSA-2168880 Scavenging of heme from plasma
R-HSA-6798695 Neutrophil degranulation
SIGNORiP00738

Miscellaneous databases

ChiTaRSiHP human
GeneWikiiHaptoglobin
GenomeRNAii3240
PROiPR:P00738
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000257017 Expressed in 210 organ(s), highest expression level in liver
CleanExiHS_HP
ExpressionAtlasiP00738 baseline and differential
GenevisibleiP00738 HS

Family and domain databases

CDDicd00033 CCP, 2 hits
cd00190 Tryp_SPc, 1 hit
InterProiView protein in InterPro
IPR008292 Haptoglobin
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR035976 Sushi/SCR/CCP_sf
IPR000436 Sushi_SCR_CCP_dom
IPR001254 Trypsin_dom
PANTHERiPTHR44686 PTHR44686, 2 hits
PfamiView protein in Pfam
PF00089 Trypsin, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
SMARTiView protein in SMART
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57535 SSF57535, 2 hits
PROSITEiView protein in PROSITE
PS50923 SUSHI, 2 hits
PS50240 TRYPSIN_DOM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHPT_HUMAN
AccessioniPrimary (citable) accession number: P00738
Secondary accession number(s): B0AZL5
, P00737, Q0VAC4, Q0VAC5, Q2PP15, Q3B7J0, Q6LBY9, Q9UC67
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 10, 2018
This is version 204 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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