Persius/hicric huggingface dataset:
KLF1
Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1  is a transcription factor that is necessary for the proper maturation of erythroid (red blood) cells.

# Structure
The molecule has two domains; the transactivation domain and the chromatin-remodeling domain. The carboxyl (C) terminal is composed of three C2H2 zinc fingers that binds to DNA, and the amino (N) terminus is proline rich and acidic.

# Function
Studies in mice first demonstrated the critical function of KLF1 in hematopoietic development. KLF1 deficient (knockout) mouse embryos exhibit a lethal anemic phenotype, fail to promote the transcription of adult -globin, and die by embryonic day 15.
Over-expression of KLF1 results in a reduction of the number of circulating platelets and hastens the onset of the -globin gene.
KLF1 coordinates the regulation of six cellular pathways that are all essential to terminal erythroid differentiation:
- Cell Membrane & Cytoskeleton
- Apoptosis
- Heme Synthesis & Transport
- Cell Cycling
- Iron Procurement
- Globin Chain Production
It has also been linked to three main processes that are all essential to transcription of the  globin gene:
- Chromatin remodeling
- Modulation of the gamma to beta globin switch
- Transcriptional activation
KLF1 binds specifically to the "CACCC" motif of the -globin gene promoter.  When natural mutations occur in the promoter, + thalassemia can arise in humans.  Thalassemia's prevalence (2 million worldwide carry the trait) makes KLF1 clinically significant.

# Clinical significance
Next-Generation sequencing efforts have revealed a surprisingly high prevalence of mutations in human KLF1. The chance of a KLF1 null child being conceived is approximately 1:24,000 in Southern China. With pre-natal blood transfusions and bone marrow transplant, it is possible to be born without KLF1. Most mutations in KLF1 lead to a recessive loss-of-function phenotype, however semi-dominant mutations have been identified in humans and mice as the cause of a rare inherited anemia CDA type IV. Additional family studies and clinical research unveiled the molecular genetics of the HPFH KLF1-related condition and established KLF1 as a novel quantitative trait locus for HbF (HBFQTL6).
KLF3
Kruppel-like factor 3 is a protein that in humans is encoded by the KLF3 gene.

# Structure
KLF3, originally termed Basic Kruppel-like Factor (BKLF), was the third member of the Kruppel-like factor family of zinc finger transcription factors to be discovered. Transcription factors in this family bind DNA by virtue of 3 characteristic three C2H2 zinc fingers at their C-termini. Since their DNA-binding domains are highly conserved within the family, all KLF proteins recognize CACCC or CGCCC boxes of the general form NCR CRC CCN, (where N is any base and R is a purine).

# Function
While the C-termini are similar in different KLFs, the N-termini vary and accordingly different KLFs can either activate or repress transcription or both. KLF3 appears to function predominantly as a repressor of transcription. It turns genes off. It does this by recruiting the C-terminal Binding Protein co-repressors CTBP1 and CTBP2. CtBP docks onto a short motif (residues 61-65) in the N-terminus of KLF3, of the general form Proline  Isoleucine  Aspartate  Leucine  Serine (the PIDLS motif). CtBP in turn recruits histone modifying enzymes to alter chromatin and repress gene expression.
KLF3 is expressed highly in the red blood cell or erythroid lineage. Here it is driven by another KLF, Erythroid KLF or KLF1, and its expression increases as erythroid cells mature. Studies in knockout mice reveal a mild anemia in the absence of functional KLF3 and the de-repression of several target genes that contain CACCC boxes in their regulatory regions. Many of these genes are activated by KLF1, hence it appears that KLF3 operates in a negative feedback loop to balance the activating potential of KLF1. KLF3 also regulates another repressive KLF, KLF8. Thus KLF1, KLF3 and KLF8 operate in a tight regulatory network. KLF3 and KLF8 may have redundant functions, as mice lacking both KLF3 and KLF8 show defects that are more severe than in either single knockout. They die in utero around day 14 of gestation.
As well as being expressed in erythroid cells, KLF3 is present in other cell types and analysis of the knockout mice has revealed defects affecting adipose tissue and B cells. KLF3 deficient mice have less adipose tissue and indications of metabolic health that may be attributable to de-repression of the adipokine hormone gene adipolin. The role of KLF3 in B lymphocytes is complex but it appears to operate in a network with KLF2 and KLF4 to influence the switch between spleen marginal zone and follicular B cells.

# Interactions
KLF3 has been shown to interact with:
- CTBP2 and
- FHL3.
KLK4
Kallikrein-related peptidase 4 is a protein which in humans is encoded by the KLK4 gene.
Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. In particular, they may serve as biomarkers for both prostate cancer and breast cancer.
This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Alternate splice variants for this gene have been described, but their biological validity has not been determined.
KLK7
Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7 gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13).

# Gene
Alternative splicing of the KLK7 gene results in two transcript variants encoding the same protein.

# Function
KLK7 is secreted as an inactive zymogen in the stratum granulosum layer of the epidermis, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by KLK5 or matriptase, which are in vitro activators of KLK7.
Once active, KLK7 is able to cleave desmocollin and corneodesmosin. These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the intermediate filaments of adjacent cells in the stratum corneum. Proteolysis of corneodesmosomes is required for desquamation, the shedding of corneocytes from the outer layer of the epidermis. This indicates a role for KLK7 in maintaining skin homeostasis.
Both KLK5 and KLK14, other skin-expressed proteases, also cleave corneodesmosomal proteins. KLK5 is able to undergo autoactivation, as well as activating KLK7 and KLK14, suggesting a KLK skin cascade is responsible for coordinating desquamation.
KLK7 activity is regulated by a number of endogenous protein inhibitors including LEKTI, SPINK6, elafin and alpha-2-Macroglobulin-like 1. Both Zn2+ and Cu2+ ions are also able to inhibit KLK7.
KLK7 is a chymotrypsin-like serine protease, preferring to cleave proteins at the residues tyrosine, phenylalanine or leucine. Analysis of peptide substrate hydrolysis indicates a strong preference for tyrosine at P1.

# Clinical significance

## Skin disease
Dysregulation of KLK7 has been linked to several skin disorders including atopic dermatitis, psoriasis and Netherton syndrome. These diseases are characterised by excessively dry, scaly and inflamed skin, due to a disruption of skin homeostasis and correct barrier function.

## Cancer
Overexpression of KLK7 may provide a route for metastasis in ovarian, breast, pancreatic, cervix, and melanoma cancers by excessive cleavage of cell junction proteins. It may also be underexpressed in lung cancer.
KLK9
Kallikrein-related peptidase 9 also known as KLK9 is an enzyme which in humans is encoded by the KLK9 gene.

# Function
KLK9 belongs to the kallikrein subgroup of serine proteases, which have diverse physiologic functions in many tissues. KLK9 is primarily expressed in thymus, testis, spinal cord, cerebellum, trachea, mammary gland, prostate, brain, salivary gland, ovary, and skin.

# Clinical significance
KLK9 is under steroid hormone regulation in ovarian and breast cancer cell lines and is a potential prognostic marker for early-stage ovarian and breast cancer patients.
Its excretion in urine has been associated with cardiac hypertrophy and aorta wall thickness, as well as some renal alterations.
KNL1
KNL1 (kinetochore scaffold 1, aka CASC5) is a protein that is encoded by the KNL1 gene in humans.

# Function
KNL1 is part of the outer kinetochore. It is a part of KMN network of proteins together with MIS12, and NDC80.
KNL1 is involved in microtubule attachment to chromosome centromeres and in the activation of the spindle checkpoint during mitosis. The CASC5 gene is upregulated in the areas of cell proliferation surrounding the ventricles during fetal brain development.

# Interactions
CASC5 has been shown to interact with MIS12, BUB1, BUBR1 and ZWINT-1.

# Polymorphisms
Homozygous polymorphisms in the CASC5 gene have been seen in patients with autosomal recessive primary microcephaly (MCPH). The mutation resulted in the skipping of exon 18 transcription, causing a frameshift and the production of a truncated protein. This truncation inhibits the binding ability of MIS12.
KTN1
Kinectin is a protein that in humans is encoded by the KTN1 gene.

# Function
Various cellular organelles and vesicles are transported along the microtubules in the cytoplasm. Likewise, membrane recycling of the endoplasmic reticulum (ER), Golgi assembly at the microtubule organizing center, and alignment of lysosomes along microtubules are all related processes. The transport of organelles requires a special class of microtubule-associated proteins (MAPs). One of these is the molecular motor kinesin (see MIM 148760 and MIM 600025), an ATPase that moves vesicles unidirectionally toward the plus end of the microtubule. Another such MAP is kinectin, a large integral ER membrane protein. Antibodies directed against kinectin have been shown to inhibit its binding to kinesin.

# Interactions
KTN1 has been shown to interact with EEF1D, RhoG and RHOA.
Ku70
Ku70  is a protein that, in humans, is encoded by the XRCC6 gene.

# Function
Together, Ku70 and Ku80 make up the Ku heterodimer, which binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair.  It is also required for V(D)J recombination, which utilizes the NHEJ pathway to promote antigen diversity in the mammalian immune system.
In addition to its role in NHEJ, Ku is also required for telomere length maintenance and subtelomeric gene silencing.
Ku was originally identified when patients with systemic lupus erythematosus were found to have high levels of autoantibodies to the protein.

# Aging
Mouse embryonic stem cells with homozygous Ku70 mutations, that is Ku70/ cells, have markedly increased sensitivity to ionizing radiation compared to heterozygous Ku70+/ or wild-type Ku70+/+ embryonic stem cells.  Mutant mice deficient in Ku70 exhibit early aging.  Using several specific criteria of aging, the mutant mice were found to display the same aging signs as control mice, but at a considerably earlier chronological age.  These results suggest that reduced ability to repair DNA double-strand breaks causes early aging, and that the wild-type Ku70 gene plays an important role in longevity assurance.  (Also see DNA damage theory of aging.)

# Nomenclature
Ku70 has been referred to by several names including:
- Lupus Ku autoantigen protein p70
- ATP-dependent DNA helicase 2 subunit 1
- X-ray repair complementing defective repair in Chinese hamster cells 6
- X-ray repair cross-complementing 6 (XRCC6)

# Interactions
Ku70 has been shown to interact with:
- CBX5,
- CHEK1,
- CREBBP,
- GCN5L2,
- HOXC4,
- Ku80,
- MRE11A,
- NCOA6,
- NCF4,
- PCNA,
- PTTG1,
- RPA2,
- TERF2,
- TERT
- VAV1,  and
- WRN.
LDB3
LIM domain binding 3 (LDB3), also known as Z-band alternatively spliced PDZ-motif (ZASP), is a protein which in humans is encoded by the LDB3 gene. ZASP belongs to the Enigma subfamily of proteins and stabilizes the sarcomere (the basic units of muscles) during contraction, through interactions with actin in cardiac and skeletal muscles. Mutations in the ZASP gene has been associated with several muscular diseases.

# Structure
ZASP is a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. ZASP interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family.
Human ZASP can exist in cardiac and skeletal cells as six distinct isoforms, based on alternative splicing of 16 exons. There are 2 ZASP short forms (Uniprot ID: O75112-6, 31.0 kDa, 283 amino acids; and Uniprot ID: O75112-5, 35.6 kDa, 330 amino acids); and 4 ZASP long forms (Uniprot ID: O75112-4, 42.8 kDa, 398 amino acids; Uniprot ID: O75112-3, 50.6 kDa, 470 amino acids; Uniprot ID: O75112-2, 66.6 kDa, 617 amino acids; and Uniprot ID: O75112, 77.1 kDa, 727 amino acids).  All ZASP isoforms have an N-terminal PDZ domain; internal, conserved sequences known as ZASP-like motifs (ZMs); and the four long isoforms have three C-terminal LIM domains.

# Function
ZASP functions to maintain structural integrity of sarcomeres during contraction, and has been shown to be involved in protein kinase A signaling. ZASP has also been shown to  co-activate 51 integrins along with the protein TLN1.

# Clinical significance
Mutations in ZASP have been associated with myofibrillar myopathy, dilated cardiomyopathy,  arrhythmogenic right ventricular cardiomyopathy, noncompaction cardiomyopathy, and muscular dystrophy.

# Interactions
The PDZ domain of ZASP binds the C-terminus of alpha actinin-2 and ZMs bind the rod domain of alpha actinin-2.  The LIM domains have been shown to interact with protein kinase C.  The cardiac-specific region of ZASP encoded by exon 4 includes a ZP motif and binds a regulatory subunit of protein kinase A.
LGI1
Leucine-rich, glioma inactivated 1, also known as LGI1, is a protein which in humans is encoded by the LGI1 gene. It may be a metastasis suppressor.

# Function
The leucine-rich glioma inactivated -1 gene is rearranged as a result of translocations in glioblastoma cell lines. The protein contains a hydrophobic segment representing a putative transmembrane domain with the amino terminus located outside the cell. It also contains leucine-rich repeats with conserved cysteine-rich flanking sequences. This gene is predominantly expressed in neural tissues and its expression is reduced in low grade brain tumors and significantly reduced or absent in malignant gliomas.

# Clinical significance
Since its earliest discovery, the LGI1 gene has been implicated in the control of cancer metastasis and in a predisposition to epilepsy. Following genetic linkage studies placing the hereditary form of autosomal dominant partial epilepsy with auditory features (ADPEAF) on chromosome region 10q24 mutation analysis of affected members in these families demonstrated LGI1 was a major cause of the disease.
More recently, LGI1 has been shown to be the major target of human autoantibodies which immunoprecipitate voltage-gated potassium channel complexes from mammalian brain tissue. LGI1 antibodies are found in patients with limbic encephalitis and in patients with faciobrachial dystonic seizures (FBDS). FBDS are a recently described form of epilepsy which is characterized by frequent, brief seizures which affect the arm and face. They appear to be preferentially responsive to immunotherapy over anti-epileptic drugs.

# Interactions
LGI1 has been shown to interact with ADAM22, and DLG4.
LGP2
Probable ATP-dependent RNA helicase DHX58 also known as RIG-I-like receptor 3 (RLR-3) or RIG-I-like receptor LGP2 (RLR) is a RIG-I-like receptor dsRNA helicase enzyme that in humans is encoded by the DHX58 gene.  The protein encoded by the gene DHX58 is known as LGP2 (Laboratory of Genetics and Physiology 2).

# Structure and function
LGP2 was first identified and characterized in the context of mammary tissue in 2001, but its function has been found to be more relevant to the field of innate antiviral immunity. LGP2 has been found to be essential for producing effective antiviral responses against many viruses that are recognized by RIG-I and MDA5.
Since LGP2 lacks CARD domains, its effect on downstream antiviral signaling is likely due to interaction with dsRNA viral ligand or the other RLRs (RIG-I and MDA5).
LGP2 has been shown to directly interact with RIG-I through its C-terminal repressor domain (RD).  The primary contact sites in this interaction is likely between the RD of LGP2 and the CARD or helicase domain of RIG-I as it is seen with RIG-I self-association, but this has not been confirmed.  The helicase activity of LGP2 has been found to be essential for its positive regulation of RIG-I signaling.  Overexpression of LGP2 is able to inhibit RIG-I-mediated antiviral signaling both in the presence and absence of viral ligands. This inhibition of RIG-I signaling is not dependent upon the ability of LGP2 to bind viral ligands and is therefore not due to ligand competition. Although LGP2 binds to dsRNA with higher affinity, it is dispensable for RIG-I-mediated recognition of synthetic dsRNA ligands.  RIG-I, when overexpressed and in LGP2 knock-down studies, has been shown to induce antiviral response in the absence of viral ligand.
LHX3
LIM/homeobox protein Lhx3 is a protein that in humans is encoded by the LHX3 gene.

# Function
LHX3 encodes a protein of a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for pituitary development and motor neuron specification. Two transcript variants encoding distinct isoforms have been identified for this gene.

# Clinical significance
Mutations in this gene have been associated with a syndrome of combined pituitary hormone deficiency and rigid cervical spine.

# Interactions
LHX3 has been shown to interact with Ldb1.
LIG4
DNA ligase 4 is an enzyme that in humans is encoded by the LIG4 gene.

# Function
The protein encoded by this gene is an ATP-dependent DNA ligase that joins double-strand breaks during the non-homologous end joining pathway of double-strand break repair.  It is also essential for V(D)J recombination.  Lig4 forms a complex with XRCC4, and further interacts with the DNA-dependent protein kinase (DNA-PK) and XLF/Cernunnos, which are also required for NHEJ.  The crystal structure of the Lig4/XRCC4 complex has been resolved. Defects in this gene are the cause of LIG4 syndrome.  The yeast homolog of Lig4 is Dnl4.

# LIG4 Syndrome
In humans, deficiency of DNA ligase 4 results in a clinical condition known as LIG4 syndrome.  This syndrome is characterized by cellular radiation sensitivity, growth retardation, developmental delay, microcephaly, facial dysmorphisms, increased disposition to leukemia, variable degrees of immunodeficiency and reduced number of blood cells.

# Haematopoietic stem cell aging
Accumulation of DNA damage leading to stem cell exhaustion is regarded as an important aspect of aging.  Deficiency of lig4 in pluripotent stem cells impairs Non-homologous end joining (NHEJ) and results in accumulation of DNA double-strand breaks and enhanced apoptosis.  Lig4 deficiency in the mouse causes a progressive loss of haematopoietic stem cells and bone marrow cellularity during aging.  The sensitivity of haematopoietic stem cells to lig4 deficiency suggests that lig4-mediated NHEJ is a key determinant of the ability of stem cells to maintain themselves against physiological stress over time.

# Interactions
LIG4 has been shown to interact with XRCC4 via its BRCT domain. This interaction stabilizes LIG4 protein in cells; cells that are deficient for XRCC4, such as XR-1 cells, have reduced levels of LIG4.

# Mechanism
LIG4 is an ATP-dependent DNA ligase.  LIG4 uses ATP to adenylate itself and then transfers the AMP group to the 5' phosphate of one DNA end.  Nucleophilic attack by the 3' hydroxyl group of a second DNA end and release of AMP yield the ligation product.   Adenylation of LIG4 is stimulated by XRCC4 and XLF.
LIM2
Lens fiber membrane intrinsic protein is a protein that in humans is encoded by the LIM2 gene.
The mammalian lens fiber cell membrane contains 5 major proteins ranging from 70 kD to 19 kD in size. The specific function of these proteins is unknown. Some of them have been shown to be involved in the formation of cataracts, e.g., crystalline-gamma-1 (CRYG1; MIM 123660). The second most abundant intrinsic membrane protein of the lens fiber cell is MP19, so named for major lens protein having a molecular weight of 19.5 kD.
This protein appears to contain 4 transmembrane domains, is a substrate for cAMP-dependent protein kinase and protein kinase C, and binds with calmodulin. Taken together, these suggest that MP19 functions in some way as a junctional component, possibly involved with lens cell communication. It has been shown to be involved with cataractogenesis.
LL37
LL-37 (or CAP-18 for cathelicidin antimicrobial peptide, 18 kDa) is a gene encoding for the only member of the human cathelicidin family. Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs), and keratinocytes. Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection.

# Clinical significance
NOTE: This article appears to be split into two parts; more on cathelicidin's clinical significance can be found on the cathelicidin page.
Patients with rosacea have elevated levels of cathelicidin. Cathelicidin is cleaved into the antimicrobial peptide LL-37 by both kallikrein 5 and kallikrein 7 serine proteases. Excessive production of LL-37 is suspected to be a contributing cause in all subtypes of Rosacea.
Higher plasma levels of LL-37, which are up-regulated by vitamin D, appear to significantly reduce the risk of death from infection in dialysis patients. Patients with a high level of LL-37 were 3.7 times more likely to survive kidney dialysis for a year without a fatal infection. Vitamin D up-regulates genetic expression of cathelicidin, which exhibits broad-spectrum microbicidal activity against bacteria, fungi, and viruses.
SAAP-148 (a synthetic antimicrobial and antibiofilm peptide) is a modified version of  LL-37 that has enhanced antimicrobial activities compared to LL-37. In particular, SAAP-148 was more efficient in killing bacteria under physiological conditions.
LMO2
LIM domain only 2 (rhombotin-like 1), also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the LMO2 gene.

# Function
LMO2 encodes a cysteine-rich, two LIM domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved.

# Clinical significance
The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number of T-cell acute lymphoblastic leukemia-specific translocations occur.

# Interactions
LMO2 has been shown to interact with:
- GATA1,
- GATA2,
- JARID1A,
- MLLT4, and
- TAL1