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Protein

Haptoglobin

Gene

Hp

Organism
Rattus norvegicus (Rat)
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 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 (By similarity).By similarity
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.By similarity

GO - Molecular functioni

  • antioxidant activity Source: UniProtKB-KW
  • hemoglobin binding Source: RGD
  • protein homodimerization activity Source: RGD

GO - Biological processi

  • acute inflammatory response Source: RGD
  • acute-phase response Source: UniProtKB-KW
  • defense response to bacterium Source: UniProtKB-KW
  • immune system process Source: UniProtKB-KW
  • liver development Source: RGD
  • organ regeneration Source: RGD
  • response to cobalamin Source: RGD
  • response to drug Source: RGD
  • response to electrical stimulus Source: RGD
  • response to glucocorticoid Source: RGD
  • response to growth hormone Source: RGD
  • response to heat Source: RGD
  • response to hypoxia Source: RGD
  • response to L-ascorbic acid Source: RGD
  • response to lead ion Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to magnesium ion Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to X-ray Source: RGD
  • spermatogenesis Source: RGD
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

ReactomeiR-RNO-2168880. Scavenging of heme from plasma.

Protein family/group databases

MEROPSiS01.972.

Names & Taxonomyi

Protein namesi
Recommended name:
Haptoglobin
Alternative name(s):
Liver regeneration-related protein LRRG173
Zonulin
Cleaved into the following 2 chains:
Gene namesi
Name:Hp
ORF Names:Ba1-647
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2825. Hp.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: RGD
  • extracellular space Source: RGD
  • Golgi apparatus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818By similarityAdd
BLAST
Chaini19 – 347329HaptoglobinPRO_0000028483Add
BLAST
Chaini19 – 10183Haptoglobin alpha chainPRO_0000028484Add
BLAST
Chaini103 – 347245Haptoglobin beta chainPRO_0000028485Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi33 – 33InterchainBy similarity
Disulfide bondi52 ↔ 86By similarity
Disulfide bondi90 ↔ 207Interchain (between alpha and beta chains)PROSITE-ProRule annotation
Glycosylationi148 – 1481N-linked (GlcNAc...)Sequence analysis
Glycosylationi152 – 1521N-linked (GlcNAc...)Sequence analysis
Disulfide bondi250 ↔ 281By similarity
Disulfide bondi292 ↔ 322By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP06866.

PTM databases

iPTMnetiP06866.

Expressioni

Tissue specificityi

Expressed by the liver and secreted in plasma.

Gene expression databases

GenevisibleiP06866. RN.

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 (By similarity).By similarity

GO - Molecular functioni

  • hemoglobin binding Source: RGD
  • protein homodimerization activity Source: RGD

Structurei

3D structure databases

ProteinModelPortaliP06866.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini31 – 8858SushiPROSITE-ProRule annotationAdd
BLAST
Domaini103 – 345243Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni259 – 2646Interaction with CD163By similarity

Domaini

The beta chain mediates most of the interactions with both subunits of hemoglobin, while the alpha chain forms the homodimeric interface.By similarity

Sequence similaritiesi

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

Keywords - Domaini

Signal, Sushi

Phylogenomic databases

HOGENOMiHOG000112945.
HOVERGENiHBG005989.
InParanoidiP06866.
KOiK16142.
OMAiWQAKMIS.
OrthoDBiEOG722J8R.
PhylomeDBiP06866.
TreeFamiTF334326.

Family and domain databases

InterProiIPR008292. Haptoglobin.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP_dom.
IPR001254. Trypsin_dom.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001137. Haptoglobin. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 1 hit.
PROSITEiPS50923. SUSHI. 1 hit.
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: P06866-1) [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
MRALGAVVTL LLWGQLFAVE LGNDATDIED DSCPKPPEIA NGYVEHLVRY
60 70 80 90 100
RCRQFYKLQT EGDGIYTLNS EKQWVNPAAG DKLPKCEAVC GKPKHPVDQV
110 120 130 140 150
QRIIGGSMDA KGSFPWQAKM ISRHGLTTGA TLISDQWLLT TAQNLFLNHS
160 170 180 190 200
ENATAKDIAP TLTLYVGKNQ LVEIEKVVLH PERSVVDIGL IKLKQKVLVT
210 220 230 240 250
EKVMPICLPS KDYVAPGRMG YVSGWGRNVN FRFTERLKYV MLPVADQEKC
260 270 280 290 300
ELHYEKSTVP EKKGAVSPVG VQPILNKHTF CAGLTKYEED TCYGDAGSAF
310 320 330 340
AVHDTEEDTW YAAGILSFDK SCAVAEYGVY VRATDLKDWV QETMAKN
Length:347
Mass (Da):38,563
Last modified:January 23, 2007 - v3
Checksum:i9DF52389AFD755D6
GO
Isoform 2 (identifier: P06866-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     89-89: V → GPTLSKNEMYTAFRSVIDFQRIVECVCVMTITYVL

Note: No experimental confirmation available.
Show »
Length:381
Mass (Da):42,475
Checksum:i9D22D28ACC1DA68B
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251A → D AA sequence (PubMed:6863267).Curated
Sequence conflicti267 – 2671S → T in AAA41348 (PubMed:2320005).Curated
Sequence conflicti267 – 2671S → T in AAA41349 (PubMed:6204979).Curated
Sequence conflicti332 – 3321R → K in AAA41348 (PubMed:2320005).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei89 – 891V → GPTLSKNEMYTAFRSVIDFQ RIVECVCVMTITYVL in isoform 2. 1 PublicationVSP_022571

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34232, M34230, M34231 Genomic DNA. Translation: AAA41348.1. Sequence problems.
AY325231 mRNA. Translation: AAP92632.1.
BC089816 mRNA. Translation: AAH89816.1.
K01933 mRNA. Translation: AAA41349.1.
PIRiA34784. HPRT.
RefSeqiNP_036714.2. NM_012582.2. [P06866-1]
UniGeneiRn.10950.

Genome annotation databases

GeneIDi24464.
KEGGirno:24464.
UCSCiRGD:2825. rat. [P06866-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34232, M34230, M34231 Genomic DNA. Translation: AAA41348.1. Sequence problems.
AY325231 mRNA. Translation: AAP92632.1.
BC089816 mRNA. Translation: AAH89816.1.
K01933 mRNA. Translation: AAA41349.1.
PIRiA34784. HPRT.
RefSeqiNP_036714.2. NM_012582.2. [P06866-1]
UniGeneiRn.10950.

3D structure databases

ProteinModelPortaliP06866.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

MEROPSiS01.972.

PTM databases

iPTMnetiP06866.

Proteomic databases

PRIDEiP06866.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24464.
KEGGirno:24464.
UCSCiRGD:2825. rat. [P06866-1]

Organism-specific databases

CTDi3240.
RGDi2825. Hp.

Phylogenomic databases

HOGENOMiHOG000112945.
HOVERGENiHBG005989.
InParanoidiP06866.
KOiK16142.
OMAiWQAKMIS.
OrthoDBiEOG722J8R.
PhylomeDBiP06866.
TreeFamiTF334326.

Enzyme and pathway databases

ReactomeiR-RNO-2168880. Scavenging of heme from plasma.

Miscellaneous databases

NextBioi603391.
PROiP06866.

Gene expression databases

GenevisibleiP06866. RN.

Family and domain databases

InterProiIPR008292. Haptoglobin.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP_dom.
IPR001254. Trypsin_dom.
[Graphical view]
PfamiPF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001137. Haptoglobin. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
SMARTiSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 1 hit.
PROSITEiPS50923. SUSHI. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structure, hormonal regulation, and identification of the interleukin-6- and dexamethasone-responsive element of the rat haptoglobin gene."
    Marinkovic S., Baumann H.
    Mol. Cell. Biol. 10:1573-1583(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Liver regeneration after PH."
    Xu C.S., Li W.Q., Li Y.C., Ma H., Wang L., Wang S.F., Han H.P., Wang G.P., Chai L.Q., Yuan J.Y., Yang K.J., Yan H.M., Chang C.F., Zhao L.F., Shi J.B., Rahman S., Wang Q.N., Zhang J.B.
    Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Liver.
  4. "Nucleotide sequence of rat haptoglobin cDNA. Characterization of the alpha beta-subunit junction region of prohaptoglobin."
    Goldstein L.A., Heath E.C.
    J. Biol. Chem. 259:9212-9217(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 76-347 (ISOFORM 1).
  5. "Biosynthesis and processing of rat haptoglobin."
    Hanley J.M., Haugen T.H., Heath E.C.
    J. Biol. Chem. 258:7858-7869(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 19-43 AND 103-127.
  6. "Comparative sequence analysis of the N-terminal region of rat, rabbit, and dog haptoglobin beta-chains."
    Kurosky A., Kim H.H., Touchstone B.
    Comp. Biochem. Physiol. 55B:453-459(1976) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 103-142.
  7. Lubec G., Afjehi-Sadat L.
    Submitted (DEC-2006) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 321-332, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Sprague-Dawley.
    Tissue: Spinal cord.

Entry informationi

Entry nameiHPT_RAT
AccessioniPrimary (citable) accession number: P06866
Secondary accession number(s): Q5EBB4, Q7TP23
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 23, 2007
Last modified: May 11, 2016
This is version 132 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.