HP

Protein identityUniProt · HPA

UniProt accession

P00738

Gene

HP

Ensembl

ENSG00000257017

Chromosome

16

Canonical length

406 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Plasma proteins, Potential drug targets, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a preproprotein, which is processed to yield both alpha and beta chains, which subsequently combine as a tetramer to produce haptoglobin. Haptoglobin functions to bind free plasma hemoglobin, which allows degradative enzymes to gain access to the hemoglobin, while at the same time preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin. Mutations in this gene and/or its regulatory regions cause ahaptoglobinemia or hypohaptoglobinemia. This gene has also been linked to diabetic nephropathy, the incidence of coronary artery disease in type 1 diabetes, Crohn's disease, inflammatory disease behavior, primary sclerosing cholangitis, susceptibility to idiopathic Parkinson's disease, and a reduced incidence of Plasmodium falciparum malaria. The protein encoded also exhibits antimicrobial activity against bacteria. A similar duplicated gene is located next to this gene on chromosome 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

Canonical amino-acid sequenceUniProt

406 residues, UniProt reviewed canonical sequence.

>P00738|HP
     1  MSALGAVIAL LLWGQLFAVD SGNDVTDIAD DGCPKPPEIA HGYVEHSVRY QCKNYYKLRT
    61  EGDGVYTLND KKQWINKAVG DKLPECEADD GCPKPPEIAH GYVEHSVRYQ CKNYYKLRTE
   121  GDGVYTLNNE KQWINKAVGD KLPECEAVCG KPKNPANPVQ RILGGHLDAK GSFPWQAKMV
   181  SHHNLTTGAT LINEQWLLTT AKNLFLNHSE NATAKDIAPT LTLYVGKKQL VEIEKVVLHP
   241  NYSQVDIGLI KLKQKVSVNE RVMPICLPSK DYAEVGRVGY VSGWGRNANF KFTDHLKYVM
   301  LPVADQDQCI RHYEGSTVPE KKTPKSPVGV QPILNEHTFC AGMSKYQEDT CYGDAGSAFA
   361  VHDLEEDTWY ATGILSFDKS CAVAEYGVYV KVTSIQDWVQ KTIAEN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

55,848 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HP.

Disease | AllUniProt

Conditions HP is implicated in, by any mechanism.

• Anhaptoglobinemia (AHP) MIM:614081

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 82 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Anhaptoglobinemia
• Hypohaptoglobinemia

Disease | ImmuneIEDB

Conditions an epitope on HP was assayed in.

• rheumatoid arthritis B cell

ReferencesPubMed · IEDB

Publications for HP from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.02

gnomAD pLI

0

gnomAD missense Z

0.01

DepMap mean gene effect

0.35

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acute-phase response
• defense response
• defense response to bacterium
• immune system process
• inflammatory response
• negative regulation of hydrogen peroxide catabolic process
• response to hydrogen peroxide
• zymogen activation

Molecular functions

• antioxidant activity
• hemoglobin binding
• serine-type endopeptidase activity

Cellular components

• blood microparticle
• endocytic vesicle lumen
• extracellular exosome
• extracellular region
• extracellular space
• haptoglobin-hemoglobin complex
• specific granule lumen
• tertiary granule lumen

Protein domainsUniProt · Pfam · InterPro

• Sushi/SCR/CCP domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• Peptidase S1, PA clan
• Sushi/SCR/CCP superfamily
• Trypsin

KeywordsUniProt

• Acute phase
• Antibiotic
• Antimicrobial
• Antioxidant
• Disulfide bond
• Glycoprotein
• Hemoglobin-binding
• Immunity
• Repeat
• Secreted
• Serine protease homolog
• Signal
• Sushi

InteractionsUniProt · HPA

Protein binding partners of HP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CD163
• ERGIC3
• APOA1