Human gene HSPA1B is an

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene. ...

-less

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

which encodes for the heat shock protein HSP70-2, a member of the

Hsp70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms. Intracellularly localized Hsp70s are an importa ...

family of proteins. The gene is located in the

major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...

, on the short arm of chromosome 6, in a cluster with two

paralogous Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

genes,

HSPA1A Heat shock 70 kDa protein 1, also termed Hsp72, is a protein that in humans is encoded by the ''HSPA1A'' gene. As a member of the heat shock protein 70 family and a chaperone protein, it facilitates the proper folding of newly translated and misfo ...

and HSPA1L. HSPA1A and HSPA1B produce nearly identical proteins because the few differences in their DNA sequences are almost exclusively synonymous substitutions or in the

three prime untranslated region In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionally ...

, heat shock 70kDa protein 1A, from

, and heat shock 70kDa protein 1B, from HSPA1B. A third, more modified

paralog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

to these genes exists in the same region, HSPA1L, which shares a 90% homology with the other two.

Function

Heat shock 70kDa protein 1B is a chaperone protein, cooperating with other heat shock proteins and chaperone systems to maintain p roteostasis by stabilizing the structural conformation of other proteins in the cell and protecting against stress-induced aggregation. Hsp70s have also been shown to bind and stabilize mRNA rich in adenine and uracil bases, independent of the occupational states of its other binding sites. This protein is deactivated by binding ATP, and activated by its dephosphorylation to ADP, which requires a potassium ion to facilitate the hydrolysis, or ATP-ADP exchange. Hsp70-2 specifically is developmentally expressed in male germ line cells during meiosis, where it is necessary for the formation of the complex between

CDC2 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...

and

cyclin B1 G2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the ''CCNB1'' gene. Function Cyclin B1 is a regulatory protein involved in mitosis. The gene product complexes with p34 (Cdk1) to form the maturation-promoting factor (MPF) ...

. It later becomes incorporated into the CatSper complex, a specialized calcium ion channel that enables spermatozoa motility.

Clinical significance

Infertility has been observed in mice when HSA1B expression is disrupted, as CDC2 in unable to form the required heterodimer with cyclin B1 for the meiotic cell cycle to progress beyond S phase. Expression of heat shock protein 70kDa protein 2 in transformed tumor cells has been implicated in the rapid proliferation,

metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

, and inhibition of

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

in ovarian, bladder urothelial, and breast cancers. Patients with chronic

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

virus infection who harbor a HSPA1B-1267

single nucleotide polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...

have a higher risk for developing

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

Interactions

Interactions have been characterized between Hsp70-2 and the following proteins: *

ATF5 Activating transcription factor 5, also known as ATF5, is a protein that, in humans, is encoded by the ''ATF5'' gene. Function First described by Nishizawa and Nagata, ATF5 has been classified as a member of the activating transcription factor ...

, *

BAG1 BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the ''BAG1'' gene. Function The oncogene BCL2 is a membrane protein that blocks a step in a pathway leading to apoptosis or programmed cell death. The protein ...

, *

BAG2 BAG family molecular chaperone regulator 2 is a protein that in humans is encoded by the ''BAG2'' gene. BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approxi ...

, *

BAG3 BAG family molecular chaperone regulator 3 is a protein that in humans is encoded by the ''BAG3'' gene. BAG3 is involved in chaperone-assisted selective autophagy. Function BAG proteins compete with Hip-1 for binding to the Hsc70/Hsp70 ATPa ...

, * CatSperβ, *

, * CHCHD3, *

DNAJC7 DnaJ homolog subfamily C member 7 is a protein that in humans is encoded by the ''DNAJC7'' gene. Interactions DNAJC7 has been shown to interact with RAD9A Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by t ...

, * DNAJC8, * DNAJC9, *

FOXP3 FOXP3 (forkhead box P3), also known as scurfin, is a protein involved in immune system responses. A member of the FOX protein family, FOXP3 appears to function as a master regulator of the regulatory pathway in the development and function of reg ...

, *

HDAC4 Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the ''HDAC4'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation ...

, *

HOPX Homeodomain-only protein is a protein that in humans is encoded by the ''HOPX'' gene. It is an important regulator of cardiac development and a marker of hippocampal neural stem cells. Function The protein encoded by this gene is a homeodomai ...

, *

HSP40 In molecular biology, chaperone DnaJ, also known as Hsp40 (heat shock protein 40 kD), is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans. Function Molecular chaperones are a diverse family o ...

, *

HSP90 Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...

, * HSP105, * IRAK1BP1, * METTL21A, * NAA10, *

NEDD1 Neural precursor cell expressed, developmentally down-regulated 1, also known as Nedd1, is a human gene and encodes the protein NEDD1. NEDD1 is localized in the centrosome and it plays a role in mitosis through its interaction with γ-tubulin. W ...

, *

NOD2 Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), is a protein that in humans is encoded by the ''NOD2'' g ...

, *

PPP5C Serine/threonine-protein phosphatase 5 is an enzyme that in humans is encoded by the ''PPP5C'' gene. Model organisms Model organisms have been used in the study of PPP5C function. A conditional knockout mouse line, called ''Ppp5ctm1a(EUCOMM) ...

, * PKRN, *

SMAD3 Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by t ...

, *

STUB1 STUB1 (STIP1 homology and U-Box containing protein 1) is a human gene that codes for the protein CHIP (C terminus of HSC70-Interacting Protein). Function The CHIP protein encoded by this gene binds to and inhibits the ATPase activity of the cha ...

, *

TERT Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of the enzyme telomerase, which, together with the telomerase RNA component (TERC), comprises the most important unit of the telomerase complex. T ...

, *

TRIM5 Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the ''TRIM5'' gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates a species-specif ...

, *

TSC2 Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the ''TSC2'' gene. Function Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is a ...

References

External links

* Heat shock proteins {{protein-stub

Function

Clinical significance

Interactions

See also

References

External links