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MACROGNATHIA

1. ACROMEGALY

Names and origin
Protein names Recommended name:
AH receptor-interacting protein
Short name=AIP
Alternative name(s):
Aryl-hydrocarbon receptor-interacting protein
HBV X-associated protein 2
Short name=XAP-2
Immunophilin homolog ARA9
Gene names Name: AIP
Synonyms: XAP2
Organism Homo sapiens (Human)
Taxonomic
identifier
9606
Taxonomic
lineage
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Ma
mmalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini
Hominidae Homo
Protein attributes
Sequence length 330 AA.
Sequence status Complete.
Protein existence Evidence at protein level
General annotation (Comments)
Function May play a positive role in AHR-mediated (aromatic hydrocarbon
receptor) signaling, possibly by influencing its receptivity for ligand
and/or its nuclear targeting.
Cellular negative regulator of the hepatitis B virus (HBV) X protein.
Subunit structure Interacts with RET in the pituitary gland; this interaction prevents the
formation of the AIP-survivin complex.
Subcellular location Cytoplasm.
Tissue specificity Widely expressed. Higher levels seen in the heart, placenta and skeletal
muscle. Not expressed in the liver.
Involvement in
disease
Growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]:
Pituitary adenomas include somatotropinoma and prolactinoma.
Note: The disease is caused by mutations affecting the gene represented
in this entry.
ACTH-secreting pituitary adenoma (ASPA) [MIM:219090]: A pituitary
adenoma resulting in excessive production of adrenocorticotropic
hormone. This leads to hypersecretion of cortisol by the adrenal glands
and ACTH-dependent Cushing syndrome. Clinical manifestations of
Cushing syndrome include facial and truncal obesity, abdominal striae,
muscular weakness, osteoporosis, arterial hypertension, diabetes.
Note: The disease is caused by mutations affecting the gene represented
in this entry.
Prolactin-secreting pituitary adenoma (PSPA) [MIM:600634]: Most
common type of hormonally active pituitary adenoma.
Note: The disease is caused by mutations affecting the gene represented
in this entry.
Sequence similarities Contains 1 PPIase FKBP-type domain.
Contains 2 TPR repeats.
Ontologies
Keywords
Cellular component Cytoplasm
Coding sequence
diversity
Polymorphism
Disease Cushing syndrome
Domain Repeat
TPR repeat
Technical term 3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
Biological_process negative regulation of cyclic-nucleotide phosphodiesterase activity
protein maturation by protein folding
protein targeting to mitochondrion
regulation of RNA biosynthetic process
regulation of protein kinase A signaling
signal transduction
xenobiotic metabolic process
Cellular_component cytoplasm
cytosol
membrane
nucleus
Molecular_function GAF domain binding
signal transducer activity
transcription coactivator activity
transcription factor binding
unfolded protein binding

2. PAGET DISEASE
Names and origin
Protein
names
Recommended name:
Sequestosome-1
Alternative name(s):
EBI3-associated protein of 60 kDa
Short name=EBIAP
Short name=p60
Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa
Ubiquitin-binding protein p62
Gene
names
Name: SQSTM1
Synonyms: ORCA, OSIL
Organism Homo sapiens (Human)
Taxonomic
identifier
9606
Taxonomic
lineage
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia
Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo
Protein attributes
Sequence length 440 AA.
Sequence status Complete.
Sequence processing The displayed sequence is further processed into a mature form.
Protein existence Evidence at protein level

General annotation (Comments)
Function Required both for the formation and autophagic degradation of polyubiquitin-
containing bodies, called ALIS (aggresome-like induced structures). Links ALIS
to the autophagic machinery via direct interaction with MAP1 LC3 family
members. May regulate the activation of NFKB1 by TNF-alpha, nerve growth
factor (NGF) and interleukin-1. May play a role in titin/TTN downstream
signaling in muscle cells. May regulate signaling cascades through
ubiquitination. Adapter that mediates the interaction between TRAF6 and
CYLD By similarity. May be involved in cell differentiation, apoptosis, immune
response and regulation of K
+
channels.
Subunit
structure
Homooligomer or heterooligomer; may form homotypic arrays. Dimerization
interferes with ubiquitin binding. Interacts directly with PRKCI and
PRKCZ Probable. Forms ternary complexes with PRKCZ and KCNAB2 or
PRKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2 and
GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and
TRAF6 By similarity. Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI,
NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM13, TRIM55 and
MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2.
Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB
through PRKCZ and PRKCI. Interacts with NGFR through TRAF6 and bridges
that complex to NTRK1. Forms a complex with MAP2K5 and PRKCZ or
PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-
alpha stimulation, interacts with RIPK1 problably bridging IKBKB to the TNF-
R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a
complex with JUB/Ajuba, PRKCZ and TRAF6. Interacts with TRAF6 and
CYLD. Identified in a complex with TRAF6 and CYLD By similarity. Identified
in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and
SQSTM1 both interact with the same ubiquitin molecule. Directly interacts with
MAP1LC3A and MAP1LC3B, as well as with other MAP1 LC3 family
members, including GABARAP, GABARAPL1 and GABARAPL2; these
interactions are necessary for the recruitment MAP1 LC3 family members to
inclusion bodies containing polyubiquitinated protein aggregates and for their
degradation by autophagy. Interacts with FHOD3. Interacts with TRMI5.
Subcellular
location
Cytoplasm. Late endosome. Lysosome. Cytoplasmic
vesicle autophagosome. Nucleus. Endoplasmic reticulum. Cytoplasm P-body.
Note: Sarcomere By similarity. In cardiac muscles localizes to the sarcomeric
band By similarity. Commonly found in inclusion bodies containing
polyubiquitinated protein aggregates. In neurodegenerative diseases, detected in
Lewy bodies in Parkinson disease, neurofibrillary tangles in Alzheimer disease,
and HTT aggregates in Huntington disease. In protein aggregate diseases of the
liver, found in large amounts in Mallory bodies of alcoholic and nonalcoholic
steatohepatitis, hyaline bodies in hepatocellular carcinoma, and in SERPINA1
aggregates. Enriched in Rosenthal fibers of pilocytic astrocytoma. In the
cytoplasm, observed in both membrane-free ubiquitin-containing protein
aggregates (sequestosomes) and membrane-surrounded autophagosomes.
Colocalizes with TRIM13 in the perinuclear endoplasmic reticulum. Co-
localizes with TRIM5 in the cytoplasmic bodies.
Tissue
specificity
Ubiquitously expressed.
Induction By proteasomal inhibitor PSI and prostaglandin J2 (PGJ2) (at protein level). By
phorbol 12-myristate 13-acetate (PMA).
Domain The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of
polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the
UBA and OPR domains are necessary and sufficient for the localization into the
ubiquitin-containing inclusion bodies.
The OPR domain mediates homooligomerization and interactions with FHOD3,
MAP2K5, NBR1, PRKCI and PRKCZ. Both the OPR and UBA domains are
necessary and sufficient for the localization into the ubiquitin-containing
inclusion bodies.
The ZZ-type zinc finger mediates the interaction with RIPK1.
Post-
translational
modification
Phosphorylated. May be phosphorylated by PRKCZ By similarity. Phosphorylated
in vitro by TTN.
Involvement
in disease
Paget disease of bone (PDB) [MIM:602080]: Metabolic bone disease affecting
the axial skeleton and characterized by focal areas of increased and disorganized
bone turn-over due to activated osteoclasts. Manifestations of the disease include
bone pain, deformity, pathological fractures, deafness, neurological
complications and increased risk of osteosarcoma. PDB is a chronic disease
affecting 2 to 3% of the population above the age of 40 years.
Note: The disease is caused by mutations affecting the gene represented in this
entry.
In a cell model for Huntington disease (HD), appears to form a shell surrounding
aggregates of mutant HTT that may protect cells from apoptosis, possibly by
recruiting autophagosomal components to the polyubiquitinated protein
aggregates.
Sequence
similarities
Contains 1 OPR domain.
Contains 1 UBA domain.
Contains 1 ZZ-type zinc finger.
Ontologies
Keywords
Biological process Apoptosis
Autophagy
Differentiation
Immunity
Cellular component Cytoplasm
Cytoplasmic vesicle
Endoplasmic reticulum
Endosome
Lysosome
Nucleus
Coding sequence
diversity
Alternative splicing
Polymorphism
Disease Disease mutation
Domain Zinc-finger
Ligand Metal-binding
Zinc
PTM Acetylation
Phosphoprotein
Technical term 3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
Biological_process apoptotic signaling pathway
autophagy
cell differentiation
endosomal transport
immune system process
intracellular signal transduction
macroautophagy
negative regulation of apoptotic process
neurotrophin TRK receptor signaling pathway
positive regulation of apoptotic process
positive regulation of protein phosphorylation
positive regulation of transcription from RNA polymerase II promoter
protein heterooligomerization
protein localization
protein phosphorylation
regulation of I-kappaB kinase/NF-kappaB signaling
regulation of Ras protein signal transduction
response to stress
ubiquitin-dependent protein catabolic process
Cellular_component aggresome
autophagic vacuole
cytoplasmic mRNA processing body
cytoplasmic vesicle
cytosol
endoplasmic reticulum
extracellular vesicular exosome
late endosome
lysosome
nucleoplasm
pre-autophagosomal structure
Molecular_function SH2 domain binding
identical protein binding
protein kinase C binding
protein kinase binding
protein serine/threonine kinase activity
receptor tyrosine kinase binding
ubiquitin binding
zinc ion binding

3. GIGANTISM
Names and origin
Protein
names
Recommended name:
Seipin
Alternative name(s):
Bernardinelli-Seip congenital lipodystrophy type 2 protein
Gene names Name: BSCL2
Organism Homo sapiens (Human)
Taxonomic
identifier
9606
Taxonomic
lineage
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammali
a Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae
Homo
Protein attributes
Sequence length 398 AA.
Sequence status Complete.
Protein existence Evidence at protein level
General annotation (Comments)
Function Is a regulator of lipid catabolism essential for adipocyte differentiation.
May also be involved in the central regulation of energy homeostasis By
similarity. Necessary for correct lipid storage and lipid droplets
maintenance; may play a tissue-autonomous role in controlling lipid
storage in adipocytes and in preventing ectopic lipid droplet formation
in non-adipose tissues.
Subcellular location Endoplasmic reticulum membrane; Multi-pass membrane protein .
Tissue specificity Expressed in motor neurons in the spinal cord and cortical neurons in
the frontal lobe (at protein level). Highly expressed in brain, testis and
adipose tissue.
Involvement in
disease
Congenital generalized lipodystrophy 2 (CGL2) [MIM:269700]: An
autosomal recessive disorder characterized by a near complete absence
of adipose tissue, extreme insulin resistance, hypertriglyceridemia,
hepatic steatosis and early onset of diabetes.
Note: The disease is caused by mutations affecting the gene represented
in this entry.
Spastic paraplegia 17, autosomal dominant (SPG17) [MIM:270685]: A
form of spastic paraplegia, a neurodegenerative disorder characterized
by a slow, gradual, progressive weakness and spasticity of the lower
limbs. Rate of progression and the severity of symptoms are quite
variable. Initial symptoms may include difficulty with balance,
weakness and stiffness in the legs, muscle spasms, and dragging the toes
when walking. In some forms of the disorder, bladder symptoms (such
as incontinence) may appear, or the weakness and stiffness may spread
to other parts of the body. SPG17 is characterized by prominent
amyotrophy of the hand muscles, the presence of mild to severe
pyramidal tract signs and spastic paraplegia. SPG17 is a motor neuron
disease overlapping with distal spinal muscular atrophy type 5.
Note: The disease is caused by mutations affecting the gene represented
in this entry.
Neuronopathy, distal hereditary motor, 5A (HMN5A) [MIM:600794]: A
disorder characterized by distal muscular atrophy mainly affecting the
upper extremities, in contrast to other distal motor neuronopathies.
These constitute a heterogeneous group of neuromuscular diseases
caused by selective degeneration of motor neurons in the anterior horn
of the spinal cord, without sensory deficit in the posterior horn. The
overall clinical picture consists of a classical distal muscular atrophy
syndrome in the legs without clinical sensory loss. The disease starts
with weakness and wasting of distal muscles of the anterior tibial and
peroneal compartments of the legs. Later on, weakness and atrophy may
expand to the proximal muscles of the lower limbs and/or to the distal
upper limbs.
Note: The disease is caused by mutations affecting the gene represented
in this entry.
Sequence similarities Belongs to the seipin family.
Ontologies
Keywords
Biological process Lipid degradation
Lipid metabolism
Cellular component Endoplasmic reticulum
Membrane
Coding sequence
diversity
Alternative splicing
Disease Congenital generalized lipodystrophy
Diabetes mellitus
Disease mutation
Hereditary spastic paraplegia
Neurodegeneration
Domain Transmembrane
Transmembrane helix
PTM Glycoprotein
Technical term Complete proteome
Reference proteome
Gene Ontology (GO)
Biological_process cell death
fat cell differentiation
lipid catabolic process
lipid particle organization
lipid storage
negative regulation of lipid catabolic process
Cellular_component integral component of endoplasmic reticulum membrane

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