Human Gene HP (uc021tld.1) Description and Page Index
  Description: Homo sapiens haptoglobin (HP), transcript variant 1, mRNA.
RefSeq Summary (NM_001126102): 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].
Transcript (Including UTRs)
   Position: hg19 chr16:72,088,508-72,094,955 Size: 6,448 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr16:72,088,552-72,094,789 Size: 6,238 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:72,088,508-72,094,955)mRNA (may differ from genome)Protein (347 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: HPT_HUMAN
DESCRIPTION: RecName: Full=Haptoglobin; AltName: Full=Zonulin; Contains: RecName: Full=Haptoglobin alpha chain; Contains: RecName: Full=Haptoglobin beta chain; Flags: Precursor;
FUNCTION: Haptoglobin combines with free plasma hemoglobin, preventing loss of iron through the kidneys and protecting the kidneys from damage by hemoglobin, while making the hemoglobin accessible to degradative enzymes.
FUNCTION: 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.
SUBUNIT: Tetramer of two alpha and two beta chains.
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
POLYMORPHISM: In the human populations there are two major allelic forms, alpha-1 with 83 residues and alpha-2 with 142 residues. These alleles determine the 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).
DISEASE: Defects in HP are the cause of anhaptoglobinemia (AHP) [MIM:614081]. AHP is a 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.
SIMILARITY: Belongs to the peptidase S1 family.
SIMILARITY: Contains 1 peptidase S1 domain.
SIMILARITY: Contains 2 Sushi (CCP/SCR) domains.
CAUTION: Although homologous to serine proteases, it has lost all essential catalytic residues and has no enzymatic activity.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HP";
WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=HP";
WEB RESOURCE: Name=Wikipedia; Note=Haptoglobin entry; URL="http://en.wikipedia.org/wiki/Haptoglobin";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HP
CDC HuGE Published Literature: HP
Positive Disease Associations: , Apolipoproteins B , atherosclerosis, coronary , cardiovascular disease , cholangitis, sclerosing Crohn's disease inflammatory bowel disease , cholangitis, sclerosing Crohn's disease ulcerative colitis , Cholesterol, LDL , cholesterol, LDL; cholesterol, total; C-reactive protein; apoA2; apoB , coronary heart disease , decreases transcriptional activity and responsiveness to interleukin-6 , diabetic nephropathy , epilepsy , haptoglobin , hepatitis C virus infection , malaria, plasmodium falciparum , myocardial infarct; cardiovascular disease , nephropathy , preeclampsia , sleep apnea
Related Studies:

  1. Mikael Ryndel , et al. Clinica chimica acta 2010 Jan, The haptoglobin 2-2 genotype is associated with carotid atherosclerosis in 64-year old women with established diabetes., Clinica chimica acta 2010 Jan. [PubMed 20064496]
  2. Apolipoproteins B
    Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903299]
    Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
  3. atherosclerosis, coronary
    Levy, A. P. et al. 2004, Haptoglobin phenotype and prevalent coronary heart disease in the Framingham offspring cohort., Atherosclerosis. 2004 Feb;172(2):361-5. [PubMed 15019547]
    These data are consistent with an interaction between Hp type and diabetes in the prevalence of CHD. These findings will need to be confirmed in other cohorts and in longitudinal studies.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: HP
Diseases sorted by gene-association score: anhaptoglobinemia* (462), plasmodium falciparum malaria (28), nutmeg liver (22), bronchopneumonia (22), favism (21), hemoglobinemia (18), glucosephosphate dehydrogenase deficiency (17), blackwater fever (16), scurvy (16), hemoglobinuria (15), intracranial vasospasm (14), autoimmune hemolytic anemia (14), chronic inflammatory demyelinating polyneuropathy (13), evans' syndrome (13), hellp syndrome (13), heme oxygenase-1 deficiency (13), pulmonary tuberculosis (11), vaginal discharge (11), malaria (11), melancholia (11), thrombotic thrombocytopenic purpura, familial (10), artery disease (10), testicular yolk sac tumor (10), dysentery (9), paroxysmal nocturnal hemoglobinuria (9), urinary schistosomiasis (9), crohn's disease (9), cryofibrinogenemia (9), chronic pulmonary heart disease (9), autoimmune disease of blood (8), endometrial disease (8), periapical granuloma (8), acquired angioedema (8), hemoglobinopathy (8), gilbert syndrome (7), congenital disorder of glycosylation, type in (7), bilirubin metabolic disorder (7), rheumatic fever (7), ceroid lipofuscinosis, neuronal, 3 (7), geniculate herpes zoster (7), cholecystitis (7), trypanosomiasis (7), thrombotic thrombocytopenic purpura, acquired (7), protein-energy malnutrition (6), methemoglobinemia (6), demyelinating polyneuropathy (6), mastitis (6), guillain-barre syndrome (6), congenital hemolytic anemia (6), prostate disease (5), congenital disorder of glycosylation, type ia (5), cataract 31, multiple types (5), hemolytic anemia (5), dirofilariasis (5), coronary artery disease (5), corticosteroid-binding globulin deficiency (5), premenstrual tension (4), epileptic encephalopathy, early infantile, 36 (4), endometritis (4), hemochromatosis (4), skeletal tuberculosis (4), fructose intolerance, hereditary (4), atransferrinemia (3), deficiency anemia (3), diabetes mellitus, insulin-dependent (1), parasitic protozoa infectious disease (1), hypertension, essential (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12257.90 RPKM in Liver
Total median expression: 12479.57 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -4.3044-0.098 Picture PostScript Text
3' UTR -45.00166-0.271 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016060 - Complement_control_module
IPR009003 - Pept_cys/ser_Trypsin-like
IPR001254 - Peptidase_S1_S6
IPR001314 - Peptidase_S1A
IPR000436 - Sushi_SCR_CCP

Pfam Domains:
PF00089 - Trypsin

SCOP Domains:
50494 - Trypsin-like serine proteases
57535 - Complement control module/SCR domain

ModBase Predicted Comparative 3D Structure on P00738
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0016209 antioxidant activity
GO:0030492 hemoglobin binding

Biological Process:
GO:0002376 immune system process
GO:0006898 receptor-mediated endocytosis
GO:0006952 defense response
GO:0006953 acute-phase response
GO:0010942 positive regulation of cell death
GO:0042542 response to hydrogen peroxide
GO:0042742 defense response to bacterium
GO:0043312 neutrophil degranulation
GO:0051354 negative regulation of oxidoreductase activity
GO:0098869 cellular oxidant detoxification
GO:2000296 negative regulation of hydrogen peroxide catabolic process

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0031838 haptoglobin-hemoglobin complex
GO:0035580 specific granule lumen
GO:0070062 extracellular exosome
GO:0071682 endocytic vesicle lumen
GO:0072562 blood microparticle
GO:1904724 tertiary granule lumen


-  Descriptions from all associated GenBank mRNAs
  AK314700 - Homo sapiens cDNA, FLJ95554, complete cds.
BC107587 - Homo sapiens haptoglobin, mRNA (cDNA clone MGC:111141 IMAGE:4734599), complete cds.
BC058031 - Homo sapiens haptoglobin, mRNA (cDNA clone MGC:61957 IMAGE:4723094), complete cds.
BC070299 - Homo sapiens haptoglobin, mRNA (cDNA clone MGC:88296 IMAGE:4716454), complete cds.
AK055872 - Homo sapiens cDNA FLJ31310 fis, clone LIVER1000165, highly similar to Haptoglobin precursor.
BC017862 - Homo sapiens haptoglobin, mRNA (cDNA clone MGC:22614 IMAGE:4700637), complete cds.
K01763 - Human haptoglobin alpha(1S)-beta precursor, mRNA.
L29394 - Homo sapiens haptoglobin alpha(2FS)-beta precursor (HP) mRNA, complete cds.
BC121124 - Homo sapiens haptoglobin, mRNA (cDNA clone MGC:150437 IMAGE:40120682), complete cds.
BC121125 - Homo sapiens haptoglobin, mRNA (cDNA clone MGC:150438 IMAGE:40120683), complete cds.
X00637 - Human mRNA FOR haptoglobin alpha 1S (Hpa 1S).
K00422 - Human haptoglobin Hp-alpha-2 mRNA, complete cds.
M13192 - Human haptoglobin Hp-alpha-2 mRNA.
KJ897003 - Synthetic construct Homo sapiens clone ccsbBroadEn_06397 HP gene, encodes complete protein.
CU691288 - Synthetic construct Homo sapiens gateway clone IMAGE:100022155 5' read HP mRNA.
JD199811 - Sequence 180835 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P00738 (Reactome details) participates in the following event(s):

R-HSA-6798749 Exocytosis of specific granule lumen proteins
R-HSA-6798745 Exocytosis of tertiary granule lumen proteins
R-HSA-2168885 Haptoglobin binds Hemoglobin
R-HSA-2168883 Haptoglobin:Hemoglobin binds CD163
R-HSA-6798695 Neutrophil degranulation
R-HSA-2168880 Scavenging of heme from plasma
R-HSA-168249 Innate Immune System
R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-168256 Immune System
R-HSA-5653656 Vesicle-mediated transport

-  Other Names for This Gene
  Alternate Gene Symbols: B0AZL5, CCDS45525, HPT_HUMAN, NM_001126102, NP_001119574, P00737, P00738, Q0VAC4, Q2PP15, Q3B7J0, Q6LBY9, Q9UC67
UCSC ID: uc021tld.1
RefSeq Accession: NM_001126102
Protein: P00738 (aka HPT_HUMAN)
CCDS: CCDS45525.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: CCDS45525.1
exon count: 5CDS single in 3' UTR: no RNA size: 1254
ORF size: 1044CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2272.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.