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VPS28 is a subunit of the ESCRT-I complex (endosomal complexes required for transport) involved in the sorting of ubiquitinated proteins. VPS28 is involved in endosomal sorting of cell surface receptors using a multivesicular body/late endosome pathway. VSP28 binding with the TSG101 may have significant roles in budding of Retroviruses, such as HIV-1 and Ebola virus.
VSP28 interacts with TSG101, VPS37B, VPS37C, FAM125A and FAM125B, and also with VPS36, this interaction mediates the association with the ESCRT-II complex. Furthermore it interacts with SNF8 and VPS25 and CEP55.

Trypsin inhibitor SPINK1 is secreted from pancreatic acinar cells into pancreatic fluid. SPINK1 has a role in inhibition of trypsin-catalyzed premature initiation of zymogens in the pancreas and the pancreatic duct. Alterations in SPINK1 gene are the cause for tropical calcific and pancreatitis hereditary pancreatitis.

Plasminogen activator inhibitor-1 is the principal inhibitor of tissue plasminogen activator(tPA) and uPA, the activators of plasminogenand hence fibrinolysis(the physiological breakdown of blood clots). It is a serine protease inhibitor(serpin) protein (SERPINE1). The other PAI, plasminogen activator inhibitor-2(PAI-2) is secreted by the placentaand only present in significant amounts during pregnancy. In addition, protease nexinacts as an inhibitor of tPA. SERPINE1, however, is the main inhibitor of the plasminogen activators.

Pirin (PIR) which belongs to the cupin superfamily, is an Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Pirin may function as a transcriptional cofactor and is involved in the regulation of DNA transcription and replication, as a result of interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein.

SERPINA1 is secreted and is a serine protease inhibitor which its targets include elastase, plasmin, collagenase, leucocytic proteases, trypsin, chymotrypsin, and plasminogen activator. Defects in SERPINA1 gene can cause emphysema or liver disease. SERPINA1 is an endogenous inhibitor of serine proteases and inhibits the catalytic domain of human recombinant matriptase in vitro. Rise in SERPINA1 occurs as an acute phase response to tissue necrosis and inflammation. mutations in SERPINA1 and SLC11A1 genes change the balance between elastase produced by leukocytes during phagocytosis.

CACYBP (calcyclin binding protein) participates in calcium-dependent ubiquitination and subsequent proteosomal degradation of target proteins. CACYBP acts as a molecular bridge in ubiquitin E3 complexes. CACYBP is involved in the ubiquitin-mediated degradation of beta-catenin.

Crk-like protein (CRKL) is a protein kinase containing SH2 and SH3 (src homology) domains which activates the RAS and JUN kinase signaling pathways and transforms fibroblasts in a RAS-dependent manner. CRKL is a substitute of the BCR-ABL tyrosine kinase, it also has a role in fibroblast transformation by BCR-ABL, and has oncogenic potential.

Alpha-parvin (PARVA) belongs to the parvin family of actin-binding proteins. PARVA has a role in the regulation of cell adhesion, cytoskeleton organization, motility and survival as well as in ciliogenesis. Parvins are related with focal contacts and contain calponin homology domains which connect to actin filaments. PARVA is extensively expressed, with the highest levels in heart, skeletal muscle, kidney and liver.

THAP3 is an element of a THAP1/THAP3-HCFC1-OGT complex which is essential for the regulation of the transcriptional activity of RRM1. THAP3 is vastly produced in placenta, skeletal muscle and heart.

VRK3 is a member of the protein kinase superfamily. The VRK3 gene has replacements at a number of residues within the ATP binding motifs which in other kinases were proved to be required for catalysis in both human and mouse. In vitro assays show that VRK3 has no phosphorylation activity but probably holds its substrate binding capability. VRK3 is universally expressed in human tissues and its protein is restricts to the nucleus.

Calcium-binding protein P22 is a phosphoprotein that binds to the sodium-hydrogen exchangers (NHEs). CHP is an essential cofactor which maintains the physiological activity of NHE family members. CHP has protein sequence resemblance to calcineurin B and it is also identified to be an endogenous inhibitor of calcineurin activity.CHP is necessary for constitutive membrane traffic. CHP Inhibits GTPase-stimulated Na(+)/H(+) exchange. CHP inhibits calcineurin phosphatase activity. Required for activity of SLC9A1/NHE1.

26S proteasome complex subunit DSS1 (SHFM1) has been suggested as a candidate gene for the autosomal dominant form of the heterogeneous limb developmental disorder split hand/split foot malformation type 1. SHFM1 is a subunit of the 26S proteasome which plays a part in ubiquitin-dependent proteolysis. SHFM1 binds and stabilizes BRCA2 and is therefore involved in the control of R-loop-associated DNA damage and thus transcription-associated genomic instability. Furthermore, SHFM1 may have a role in the completion of the cell cycle. SHFM1 is a component of the TREX-2 complex (transcription and export complex 2), comprised of at least ENY2, GANP, PCID2, DSS1, and either centrin CETN2 or CETN3.

Pleckstrin homology-like domain family A member 2 (PHLDA2) is a cytoplasmic protein, which is involved in fetal and placental growth. PHLDA2 is an apoptosis-related protein, which acts as a negative growth regulator and is expressed during normal human development. PHLDA2 is imprinted on placenta, liver and fetal tissues during embryogenesis and is removed once development is complete. The PHLDA2 gene is one of a number of genes in the imprinted gene domain of 11p15.5 which is considered to be an important tumor suppressor gene region. Changes in this region may be linked to the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. PHLDA2 is expressed in placenta (present in all cells of the villous cytotrophoblast) and adult prostate gland. Furthermore, PHLDA2 is expressed in adult brain and neuroblastoma, medullablastoma and glioblastoma cell lines and at low levels in adult liver and lung, and fetal liver.

AMRC10 is a protein which contains an armadillo repeat and transmembrane domain. Upregulation of the AMRC10 gene has a role in hepatocellular carcinoma. AMRC10 decreases the transcriptional activity of the tumor suppressor protein p53 through direct interaction with the DNA-binding domain of p53, moreover it might play a role in cell growth and survival.

Pallidin is involved in intracellular vesicle trafficking. PLDN cooperates with Syntaxin 13 that facilitates intracellular membrane fusion. A Few alternatively spliced transcript variations of this gene have been discovered however the full-length nature of several of these variants has not been determined. PLDN takes part in the creation of lysosome-related organelles, for example melanosomes and platelet-dense granules. PLDN is known to cooperate with Dysbindin, BLOC1S1, STX12, CNO, MUTED, SNAPAP and BLOC1S2.

E3 ubiquitin-protein ligase RNF181 (RNF181) accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the thioester form and subsequently directly transfers the ubiquitin to targeted substrates. RNF181 is widely expressed, with the highest levels in the liver and heart and the lowest levels in the brain and skeletal muscle. RNF181 is also expressed in platelets (at protein level).

SNRPD3 is a small nuclear ribonucleoprotein (snRNPs) that contains the spliceosome in eukaryotes. SNRPD3 is essential for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Alternative splicing happens in this locus and two transcript variants encoding the same protein were branded.

SIL1 is localized to endoplasmic reticulum (ER). SIL1 is an N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. SIL1 acts as a nucleotide exchange factor for another unfolded protein response protein. Mutations in SIL1 are linked to Marinesco-Sjogren syndrome.

DENR takes part in the translation of target mRNAs by scanning and recognizing the initiation codon. DENR protein is involved in the intonation of the translational profile of a subset of cancer-related mRNAs when engaged to the translational initiation complex by the oncogene MCTS1.

The protein kinase A holoenzyme is a heterotetramer composed of two types of subunits: Catalytic and Regulatory. The Catalyticsubunit contains the enzyme's active site. It also contains a domain that binds ATP and a domain that binds the regulatory subunit. The Regulatory subunit consists oftwo molecules which bind one another in an anti-parallel orientation to form a homodimer; for type I subunits- this binding is covalent via disulfide bonds. This subunit also has has two domains that bind cyclic AMP, a domain that interacts with a catalytic subunit, and an "auto-inhibitory" domain that serves as a substrate or pseudosubstrate for the catalytic subunit. Regulatory subunits may also have biologic activity distinct from their role in modulating catalytic subunit activity. Regulatory subunits exist in two major forms, RI and RII, with each form having two subtypes designated alpha and beta. Each of the four isotypes of the regulatory subunit is encoded by a different gene. In addition, three isotypes of the catalytic subunit have been identified (alpha, beta and gamma). The different isotypes tend to have different distributions within cells and among tissues. Type I enzymes inhabit cytoplasmic, soluble fractions of the cell, whereas type II enzymes tend to associate with cellular membranes.

RQCD1 is a novel transcriptional cofactor which mediates retinoic acid-induced cell differentiation. RQCD1 down-regulates MYB- and JUN-dependent transcription and may have a role in cell differentiation. RQCD1 also has a role in retinoic acid-controlled lung development.

OTOR proteins is also known as fibrocyte-derived protein (Fdp) and Melanoma inhibitory activity-like (MIAL). Otoraplin is a member of the melanoma-inhibiting activity gene family. Otoraplin is a secreted 16 kDa globular protein that is expressed in the inner ear by periotic mesenchyme and developing and mature fibrocytes. OTOR is highly homologous to MIA/cartilage-derived retinoic acid-sensitive protein (CD-RAP), which is a cartilage-specific protein that is also expressed in malignant melanoma cells. The 111 amino acid mature human otoraplin contains 1 SH3 domain (46 – 107 amino acids) and a Tyr at position 50 that is reportedly sulfated. Otoraplin takes pasrt in the initiation of periotic mesenchyme chondrogenesis.
Otoraplin is secreted through the Golgi apparatus and plays a role in cartilage development and maintenance. A frequent polymorphism in the translation start codon of OTOR can abolish translation and may be associated with forms of deafness.

Proteasome 26S Subunit, Non-ATPase 5, also known as PSMD5 is a member of the proteasome subunit S5B/HSM3 family. The 26S proteasome is an enzymatic complex which degrades ubiquitinated proteins in eukaryotic cells. Furthermore, PSMD5 acts as a chaperones which is involved in the assembly of the 26s proteasome, particularly of the base subcomplex of the PA700/19S regulatory complex. PSMD5 is full of dileucine repeats, which have been involved in trafficking of various transmembrane proteins.