Havcr1

Havcr1 Full Name

hepatitis A virus cellular receptor 1

Havcr1 Introduction

Hepatitis A virus cellular receptor 1 (HAVCR1), also widely recognized in scientific literature as Kidney Injury Molecule-1 (KIM-1) or T-cell immunoglobulin and mucin domain 1 (TIM-1), is a versatile type I transmembrane glycoprotein. Initially discovered as the essential cellular entry receptor for the Hepatitis A virus, HAVCR1 is now understood to play multifaceted roles spanning immunology, virology, and nephrology. Structurally characterized by an N-terminal immunoglobulin (Ig)-like variable domain and a heavily glycosylated mucin domain, HAVCR1 functions primarily as a phosphatidylserine receptor. This allows the protein to specifically recognize and bind to apoptotic cells, effectively mediating the clearance of dead cells and necrotic debris through phagocytosis. In the immune system, HAVCR1 is preferentially expressed on activated CD4+ T cells, where it provides costimulatory signals that drive T-helper 2 (Th2) cell differentiation, thereby modulating the adaptive immune response and maintaining peripheral tolerance.

Figure 1. The structure of TIM and the binding to PtdSer. (Source: Wang J, et al. 2022)

Clinically, the most prominent and transformative application of HAVCR1 lies in the field of nephrology. In healthy adult kidneys, HAVCR1 expression is virtually undetectable. However, immediately following ischemic or nephrotoxic Acute Kidney Injury (AKI), it undergoes massive and rapid upregulation on the apical membrane of surviving proximal tubule epithelial cells. During this pathological process, the extracellular domain of HAVCR1 is actively cleaved by metalloproteinases and shed into the tubular lumen. Consequently, urinary KIM-1 has emerged as an FDA-qualified, highly sensitive, and non-invasive early biomarker for AKI, significantly outperforming traditional functional markers like serum creatinine in detecting early-stage renal damage.

Beyond renal injury, HAVCR1 is a critical factor in infectious diseases and oncology. Due to its affinity for phosphatidylserine, which is often present on viral envelopes, HAVCR1 acts as a potent entry enhancer for numerous highly pathogenic enveloped viruses, including Ebola, Marburg, Dengue, and Zika viruses. Furthermore, because of its intrinsic role in skewing immune responses toward a Th2 profile, genetic polymorphisms in the HAVCR1 gene are strongly associated with increased susceptibility to atopic conditions such as asthma and allergic rhinitis. In oncology, aberrant overexpression of HAVCR1 is frequently observed in clear cell renal cell carcinoma (ccRCC) and ovarian cancer, where it promotes tumor cell survival, modulates the tumor microenvironment, and serves as a potential prognostic indicator and therapeutic target.

Alternate Names for Havcr1

HAVCR1; hepatitis A virus cellular receptor 1; TIM; KIM1; TIM1; HAVCR; KIM-1; TIM-1; TIMD1; TIMD-1; HAVCR-1; kidney injury molecule 1; T-cell membrane protein 1; T-cell immunoglobulin mucin receptor 1; T-cell immunoglobulin mucin family member 1; T cell immunoglobin domain and mucin domain protein 1; ARD5

• 1. Wang J, et al. The role of phosphatidylserine on the membrane in immunity and blood coagulation. Biomark Res. 2022 Jan 15;10(1):4.
  2. Kondratowicz AS, et al. T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus. Proc Natl Acad Sci U S A. 2011 May 17;108(20):8426-31.