value: Receptor-type tyrosine-protein phosphatase N2

value: Islet cell autoantigen-related protein

value: IAR

value: ICAAR

value: Phogrin

flag: Precursor

value: Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (By similarity). Required to maintain normal levels of renin expression and renin release (By similarity). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate (By similarity). Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolysis of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments (PubMed:26620550)

commentType: FUNCTION

name: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

database: Rhea

commentType: BIOPHYSICOCHEMICAL PROPERTIES

value: Optimum pH is 4.5.

value: Self-associates. Interacts (via cytoplasmic domain) with PTPRN (via cytoplasmic domain). Interacts (precursor form) with CPE. Interacts with HAP1. Interacts with AP2A1 or AP2A2 and AP1G1; indicative for an association with adaptor protein complex 2 (AP-2) and adaptor protein complex 1 (AP-1) (By similarity). Interacts with AP2M1; indicative for an association with adaptor protein complex 2 (AP-2). Interacts with MYO5A (By similarity)

value: Predominantly found on dense-core secretory granules. Sorting to secretory granules in part is dependent of the N-terminal propeptide domain of the precursor and its interaction with CPE (By similarity). Transiently found at the cell membrane, when secretory vesicles fuse with the cell membrane to release their cargo. Is then endocytosed and recycled to secretory vesicles involving clathrin-dependent AP2-mediated endocytosis. Recycled via STX6- but not TTTGN1/TGN38-containing compartments (By similarity)

value: Cytoplasmic vesicle, secretory vesicle membrane

value: Single-pass type I membrane protein

value: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane

value: Highest levels in brain and pancreas (PubMed:8798755, PubMed:8954911). Lower levels in trachea, prostate, stomach and spinal cord (PubMed:8798755)

value: The cytoplasmic domain appears to contain the autoantigenic epitopes

value: The leucine-based sorting signal is proposed to function in trafficking at the plasma membrane

value: The tyrosine-based internalization signal is proposed to function at the level of clathrin-mediated endocytosis and recycling

value: Subject to proteolytic cleavage at multiple sites

value: Autoantigen in insulin-dependent diabetes mellitus (IDDM)

value: Belongs to the protein-tyrosine phosphatase family. Receptor class 8 subfamily

value: Has no tyrosine-protein phosphatase activity at mild acidic conditions (pH 5.5). The in vivo relevance of the low PPase activity at acidic conditions (pH 4.5) is questioned. This catalytic activity seems to be affected by the replacement of a highly conserved residue in the tyrosine-protein phosphatase domain

type: Signal

description: Extracellular

description: Helical

description: Cytoplasmic

description: Tyrosine-protein phosphatase

description: Involved in localization to secretory granules; interaction with CPE

description: Disordered

description: Disordered

description: Disordered

description: Disordered

description: Disordered

description: Tyrosine-based internalization motif

description: Leucine-based sorting signal

description: Basic and acidic residues

description: Polar residues

description: Low complexity

description: Phosphocysteine intermediate

description: Cleavage

description: Phosphoserine

description: Phosphoserine

description: Phosphoserine

description: Phosphoserine

description: N-linked (GlcNAc...) asparagine

description: in isoform 3

description: in isoform 4

description: in isoform 2

description: in dbSNP:rs3800855

description: in dbSNP:rs1130495

description: in dbSNP:rs1130496

description: in dbSNP:rs1130499

description: in dbSNP:rs3752368

description: in dbSNP:rs7456452

description: in a colorectal cancer sample; somatic mutation; dbSNP:rs577236042

description: No effect to increase invasion, migration, and metastatic lung colonization in mice breast cancer model.

description: Loss of activity.

description: in Ref. 4; AAB68603

description: in Ref. 2; CAA69880

description: in Ref. 2; CAA69880

title: Molecular cloning and characterization of the human transmembrane protein tyrosine phosphatase homologue, phogrin, an autoantigen of type 1 diabetes.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
DOMAIN
ROLE IN DIABETES MELLITUS
VARIANT PRO-208

authors:
Smith P.D.
Barker K.T.
Wang J.
Lu Y.-J.
Shipley J.
Crompton M.R.

title: ICAAR, a novel member of a new family of transmembrane, tyrosine phosphatase-like proteins.

referencePositions: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1)

authors:
Cui L.
Yu W.-P.
de Aizpurua H.J.
Schmidli R.S.
Pallen C.J.

title: Cloning and characterization of islet cell antigen-related protein-tyrosine phosphatase (PTP), a novel receptor-like PTP and autoantigen in insulin-dependent diabetes.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
CATALYTIC ACTIVITY
BIOPHYSICOCHEMICAL PROPERTIES
TISSUE SPECIFICITY
ROLE IN DIABETES MELLITUS

authors:
Jiang S.
Tulloch G.
Fu Y.
London R.
Hummel G.S.
White R.A.
Avraham H.
Avraham S.

title: Characterization and chromosomal localization of PTPRP, a receptor protein tyrosine phosphatase predominantly expressed in brain and pancreas.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4)
VARIANTS THR-140; PRO-208 AND ASN-325

authors:
Nagase T.
Ishikawa K.
Nakajima D.
Ohira M.
Seki N.
Miyajima N.
Tanaka A.
Kotani H.
Nomura N.
Ohara O.

title: Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3)

authors:
Nakajima D.
Okazaki N.
Yamakawa H.
Kikuno R.
Ohara O.
Nagase T.

title: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.

authors:
Hillier L.W.
Fulton R.S.
Fulton L.A.
Graves T.A.
Pepin K.H.
Wagner-McPherson C.
Layman D.
Maas J.
Jaeger S.
Walker R.
Wylie K.
Sekhon M.
Becker M.C.
O'Laughlin M.D.
Schaller M.E.
Fewell G.A.
Delehaunty K.D.
Miner T.L.
Nash W.E.
Cordes M.
Du H.
Sun H.
Edwards J.
Bradshaw-Cordum H.
Ali J.
Andrews S.
Isak A.
Vanbrunt A.
Nguyen C.
Du F.
Lamar B.
Courtney L.
Kalicki J.
Ozersky P.
Bielicki L.
Scott K.
Holmes A.
Harkins R.
Harris A.
Strong C.M.
Hou S.
Tomlinson C.
Dauphin-Kohlberg S.
Kozlowicz-Reilly A.
Leonard S.
Rohlfing T.
Rock S.M.
Tin-Wollam A.-M.
Abbott A.
Minx P.
Maupin R.
Strowmatt C.
Latreille P.
Miller N.
Johnson D.
Murray J.
Woessner J.P.
Wendl M.C.
Yang S.-P.
Schultz B.R.
Wallis J.W.
Spieth J.
Bieri T.A.
Nelson J.O.
Berkowicz N.
Wohldmann P.E.
Cook L.L.
Hickenbotham M.T.
Eldred J.
Williams D.
Bedell J.A.
Mardis E.R.
Clifton S.W.
Chissoe S.L.
Marra M.A.
Raymond C.
Haugen E.
Gillett W.
Zhou Y.
James R.
Phelps K.
Iadanoto S.
Bubb K.
Simms E.
Levy R.
Clendenning J.
Kaul R.
Kent W.J.
Furey T.S.
Baertsch R.A.
Brent M.R.
Keibler E.
Flicek P.
Bork P.
Suyama M.
Bailey J.A.
Portnoy M.E.
Torrents D.
Chinwalla A.T.
Gish W.R.
Eddy S.R.
McPherson J.D.
Olson M.V.
Eichler E.E.
Green E.D.
Waterston R.H.
Wilson R.K.

title: The DNA sequence of human chromosome 7.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)

authors:
Lu J.
Li Q.
Xie H.
Chen Z.-J.
Borovitskaya A.E.
Maclaren N.K.
Notkins A.L.
Lan M.S.

title: Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment.

authors:
Choudhary C.
Kumar C.
Gnad F.
Nielsen M.L.
Rehman M.
Walther T.C.
Olsen J.V.
Mann M.

title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

referencePositions: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-970

referencePositions: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]

authors:
Sengelaub C.A.
Navrazhina K.
Ross J.B.
Halberg N.
Tavazoie S.F.

title: PTPRN2 and PLCbeta1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling.

authors:
Barr A.J.
Ugochukwu E.
Lee W.H.
King O.N.F.
Filippakopoulos P.
Alfano I.
Savitsky P.
Burgess-Brown N.A.
Mueller S.
Knapp S.

title: Large-scale structural analysis of the classical human protein tyrosine phosphatome.

referencePositions: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 715-1010

authors:
Noguera M.E.
Primo M.E.
Jakoncic J.
Poskus E.
Solimena M.
Ermacora M.R.

title: X-ray structure of the mature ectodomain of phogrin.

referencePositions: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 502-599

authors:
Sjoeblom T.
Jones S.
Wood L.D.
Parsons D.W.
Lin J.
Barber T.D.
Mandelker D.
Leary R.J.
Ptak J.
Silliman N.
Szabo S.
Buckhaults P.
Farrell C.
Meeh P.
Markowitz S.D.
Willis J.
Dawson D.
Willson J.K.V.
Gazdar A.F.
Hartigan J.
Wu L.
Liu C.
Parmigiani G.
Park B.H.
Bachman K.E.
Papadopoulos N.
Vogelstein B.
Kinzler K.W.
Velculescu V.E.

title: The consensus coding sequences of human breast and colorectal cancers.

value: the signaling adaptor protein karap/dap12/tyrobp (sap-kdt) family

value: 4 GO annotations based on evolutionary models

value: Expressed in lateral nuclear group of thalamus and 185 other cell types or tissues

value: F:transmembrane receptor protein tyrosine phosphatase activity

value: P:insulin secretion involved in cellular response to glucose stimulus

value: receptor-type tyrosine-protein phosphatase-like N isoform X1

value: receptor-type tyrosine-protein phosphatase-like N isoform X2

value: Protein tyrosine phosphatase superfamily

value: Protein-tyrosine phosphatase receptor IA-2 ectodomain

value: IA-2 PROTEIN TYROSINE PHOSPHATASE, ISOFORM C

value: RECEPTOR-TYPE TYROSINE-PROTEIN PHOSPHATASE N2

value: (Phosphotyrosine protein) phosphatases II


entryType: UniProtKB reviewed (Swiss-Prot)

scientificName: Drosophila melanogaster

commonName: Fruit fly

lineage: Eukaryota Metazoa Ecdysozoa Arthropoda Altocrustacea Allotriocarida Hexapoda Insecta Pterygota Neoptera Eumetabola Endopterygota Aparaglossata Panorpida Diptera Brachycera Muscomorpha Ephydroidea Drosophilidae Drosophila Sophophora

proteinExistence: 2: Evidence at transcript level

source: UniProtKB

value: Glycosaminoglycan xylosylkinase homolog

value: Xylose kinase homolog

source: FlyBase

value: Kylose kinase that mediates the 2-O-phosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans

commentType: CATALYTIC ACTIVITY

name: 3-O-(beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-xylosyl)-L-seryl-[protein] + ATP = 3-O-(beta-D-galactosyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-2-O-phosphoxylosyl)-L-seryl-[protein] + ADP + H(+)

database: ChEBI

commentType: COFACTOR

commentType: SUBCELLULAR LOCATION

source: PubMed

value: Golgi apparatus

value: Endoplasmic reticulum

value: Belongs to the FAM20 family

commentType: SIMILARITY

modifier: EXACT

type: Chain

description: Glycosaminoglycan xylosylkinase homolog

type: Active site

type: Binding site

type: Glycosylation

description: N-linked (GlcNAc...) asparagine

source: PROSITE-ProRule

type: Disulfide bond

ATP-binding

category: Ligand

Disulfide bond

category: PTM

authors:
Adams M.D.
Celniker S.E.
Holt R.A.
Evans C.A.
Gocayne J.D.
Amanatides P.G.
Scherer S.E.
Li P.W.
Hoskins R.A.
Galle R.F.
George R.A.
Lewis S.E.
Richards S.
Ashburner M.
Henderson S.N.
Sutton G.G.
Wortman J.R.
Yandell M.D.
Zhang Q.
Chen L.X.
Brandon R.C.
Rogers Y.-H.C.
Blazej R.G.
Champe M.
Pfeiffer B.D.
Wan K.H.
Doyle C.
Baxter E.G.
Helt G.
Nelson C.R.
Miklos G.L.G.
Abril J.F.
Agbayani A.
An H.-J.
Andrews-Pfannkoch C.
Baldwin D.
Ballew R.M.
Basu A.
Baxendale J.
Bayraktaroglu L.
Beasley E.M.
Beeson K.Y.
Benos P.V.
Berman B.P.
Bhandari D.
Bolshakov S.
Borkova D.
Botchan M.R.
Bouck J.
Brokstein P.
Brottier P.
Burtis K.C.
Busam D.A.
Butler H.
Cadieu E.
Center A.
Chandra I.
Cherry J.M.
Cawley S.
Dahlke C.
Davenport L.B.
Davies P.
de Pablos B.
Delcher A.
Deng Z.
Mays A.D.
Dew I.
Dietz S.M.
Dodson K.
Doup L.E.
Downes M.
Dugan-Rocha S.
Dunkov B.C.
Dunn P.
Durbin K.J.
Evangelista C.C.
Ferraz C.
Ferriera S.
Fleischmann W.
Fosler C.
Gabrielian A.E.
Garg N.S.
Gelbart W.M.
Glasser K.
Glodek A.
Gong F.
Gorrell J.H.
Gu Z.
Guan P.
Harris M.
Harris N.L.
Harvey D.A.
Heiman T.J.
Hernandez J.R.
Houck J.
Hostin D.
Houston K.A.
Howland T.J.
Wei M.-H.
Ibegwam C.
Jalali M.
Kalush F.
Karpen G.H.
Ke Z.
Kennison J.A.
Ketchum K.A.
Kimmel B.E.
Kodira C.D.
Kraft C.L.
Kravitz S.
Kulp D.
Lai Z.
Lasko P.
Lei Y.
Levitsky A.A.
Li J.H.
Li Z.
Liang Y.
Lin X.
Liu X.
Mattei B.
McIntosh T.C.
McLeod M.P.
McPherson D.
Merkulov G.
Milshina N.V.
Mobarry C.
Morris J.
Moshrefi A.
Mount S.M.
Moy M.
Murphy B.
Murphy L.
Muzny D.M.
Nelson D.L.
Nelson D.R.
Nelson K.A.
Nixon K.
Nusskern D.R.
Pacleb J.M.
Palazzolo M.
Pittman G.S.
Pan S.
Pollard J.
Puri V.
Reese M.G.
Reinert K.
Remington K.
Saunders R.D.C.
Scheeler F.
Shen H.
Shue B.C.
Siden-Kiamos I.
Simpson M.
Skupski M.P.
Smith T.J.
Spier E.
Spradling A.C.
Stapleton M.
Strong R.
Sun E.
Svirskas R.
Tector C.
Turner R.
Venter E.
Wang A.H.
Wang X.
Wang Z.-Y.
Wassarman D.A.
Weinstock G.M.
Weissenbach J.
Williams S.M.
Woodage T.
Worley K.C.
Wu D.
Yang S.
Yao Q.A.
Ye J.
Yeh R.-F.
Zaveri J.S.
Zhan M.
Zhang G.
Zhao Q.
Zheng L.
Zheng X.H.
Zhong F.N.
Zhong W.
Zhou X.
Zhu S.C.
Zhu X.
Smith H.O.
Gibbs R.A.
Myers E.W.
Rubin G.M.
Venter J.C.

title: The genome sequence of Drosophila melanogaster.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]

authors:
Misra S.
Crosby M.A.
Mungall C.J.
Matthews B.B.
Campbell K.S.
Hradecky P.
Huang Y.
Kaminker J.S.
Millburn G.H.
Prochnik S.E.
Smith C.D.
Tupy J.L.
Whitfield E.J.
Bayraktaroglu L.
Berman B.P.
Bettencourt B.R.
Celniker S.E.
de Grey A.D.N.J.
Drysdale R.A.
Harris N.L.
Richter J.
Russo S.
Schroeder A.J.
Shu S.Q.
Stapleton M.
Yamada C.
Ashburner M.
Gelbart W.M.
Rubin G.M.
Lewis S.E.

title: Annotation of the Drosophila melanogaster euchromatic genome: a systematic review.

authors:
Stapleton M.
Carlson J.W.
Brokstein P.
Yu C.
Champe M.
George R.A.
Guarin H.
Kronmiller B.
Pacleb J.M.
Park S.
Wan K.H.
Rubin G.M.
Celniker S.E.

title: A Drosophila full-length cDNA resource.

authors:
Ishikawa H.O.
Xu A.
Ogura E.
Manning G.
Irvine K.D.

title: The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins.

value: Glycosaminoglycan-protein linkage region biosynthesis

value: Expressed in posterior terminal follicle cell in ovary and 85 other cell types or tissues

value: F:phosphotransferase activity, alcohol group as acceptor

value: F:protein serine/threonine kinase activity


scientificName: Homo sapiens

commonName: Human

lineage: Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Haplorrhini Catarrhini Hominidae Homo

proteinExistence: 1: Evidence at protein level

value: Metalloprotease-related protein 1

value: Overlapping with the m-AAA protease 1 homolog

source: HGNC

value: Metalloprotease that is part of the quality control system in the inner membrane of mitochondria (PubMed:20038677, PubMed:25605331, PubMed:32132706, PubMed:32132707). Activated in response to various mitochondrial stress, leading to the proteolytic cleavage of target proteins, such as OPA1, UQCC3 and DELE1 (PubMed:20038677, PubMed:25275009, PubMed:32132706, PubMed:32132707). Involved in the fusion of the mitochondrial inner membranes by mediating cleavage of OPA1 at S1 position, generating the soluble OPA1 (S-OPA1), which cooperates with the membrane form (L-OPA1) to coordinate the fusion of mitochondrial inner membranes (PubMed:31922487). Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1, leading to excess production of soluble OPA1 (S-OPA1) and negative regulation of mitochondrial fusion (PubMed:20038677, PubMed:25275009). Involved in mitochondrial safeguard in response to transient mitochondrial membrane depolarization (flickering) by catalyzing cleavage of OPA1, leading to excess production of S-OPA1, preventing mitochondrial hyperfusion (By similarity). Also acts as a regulator of apoptosis: upon BAK and BAX aggregation, mediates cleavage of OPA1, leading to the remodeling of mitochondrial cristae and allowing the release of cytochrome c from mitochondrial cristae (PubMed:25275009). In depolarized mitochondria, may also act as a backup protease for PINK1 by mediating PINK1 cleavage and promoting its subsequent degradation by the proteasome (PubMed:30733118). May also cleave UQCC3 in response to mitochondrial depolarization (PubMed:25605331). Also acts as an activator of the integrated stress response (ISR): in response to mitochondrial stress, mediates cleavage of DELE1 to generate the processed form of DELE1 (S-DELE1), which translocates to the cytosol and activates EIF2AK1/HRI to trigger the ISR (PubMed:32132706, PubMed:32132707). Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions (By similarity). Binds cardiolipin, possibly regulating its protein turnover (By similarity). Required for the stability of the respiratory supercomplexes (By similarity)

value: Binds 1 zinc ion per subunit.

value: Protease activity is activated upon autocatalytic cleavage in response to mitochondrial depolarization

commentType: ACTIVITY REGULATION

value: Homooligomer

commentType: SUBUNIT

value: Mitochondrion inner membrane

value: Single-pass membrane protein

commentType: ALTERNATIVE PRODUCTS

isoformSequenceStatus: Displayed

isoformSequenceStatus: Described

value: Widely expressed, with strong expression in the heart, skeletal muscle, kidney and liver

commentType: TISSUE SPECIFICITY

value: The stress-sensor region regulates proteolysis and activation

commentType: DOMAIN

value: May form a redox-dependent disulfide bond (By similarity). Exists in a semi-oxidized state and is activated by prolonged hypoxia (PubMed:31044600)

commentType: PTM

value: Autocatalytically cleaved in response to mitochondrial depolarization both at the N-terminus and C-terminus to generate the short active form (S-OMA1) (By similarity). Autocatalytic processing at the C-terminus takes place at residues 447-456 (By similarity). The S-OMA1 form is unstable (By similarity). OMA1 pre-processing by AFG3L2 may participate in maturation before OMA1 autocatalytic cleavage (PubMed:29545505). Degraded by YMEL1 in response to membrane depolarization (PubMed:26923599). Protein turnover is regulated by prohibitin (PHB and PHB2), which promotes degradation of OMA1 in a cardiolipin-binding manner (By similarity)

value: Belongs to the peptidase M48 family

value: Was initially reported to localize in the endoplasmic reticulum (PubMed:12886954). However, it was later shown that it localizes to mitochondrion (PubMed:20038677)

commentType: CAUTION

commentType: SEQUENCE CAUTION

sequenceCautionType: Erroneous initiation

note: Truncated N-terminus.

type: Transit peptide

description: Mitochondrion

type: Propeptide

modifier: UNKNOWN

description: Metalloendopeptidase OMA1, mitochondrial

type: Topological domain

description: Mitochondrial matrix

type: Transmembrane

description: Helical

description: Mitochondrial intermembrane

type: Region

description: Cardiolipin-binding

description: Stress-sensor region

description: in isoform 2

description: in dbSNP:rs34466938

description: in a patient with amyotrophic lateral sclerosis; dbSNP:rs75220198

description: in dbSNP:rs17117720

description: in dbSNP:rs17117699

description: in a colorectal cancer sample; somatic mutation

description: in a patient with amyotrophic lateral sclerosis; dbSNP:rs139938730

description: in dbSNP:rs17117678

description: in dbSNP:rs77980955

description: Abolished protease activity and ability to mediate cleavage of DELE1 in response to mitochondrial stress. Abolished ability to mediate cleavage of PINK1 in depolarized mitochondria.

description: Abolishes ability to cleave OPA1 at S1 position.

authors:
Bao Y.-C.
Tsuruga H.
Hirai M.
Yasuda K.
Yokoi N.
Kitamura T.
Kumagai H.

title: Identification of a human cDNA sequence which encodes a novel membrane-associated protein containing a zinc metalloprotease motif.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
TISSUE SPECIFICITY

authors:
Gregory S.G.
Barlow K.F.
McLay K.E.
Kaul R.
Swarbreck D.
Dunham A.
Scott C.E.
Howe K.L.
Woodfine K.
Spencer C.C.A.
Jones M.C.
Gillson C.
Searle S.
Zhou Y.
Kokocinski F.
McDonald L.
Evans R.
Phillips K.
Atkinson A.
Cooper R.
Jones C.
Hall R.E.
Andrews T.D.
Lloyd C.
Ainscough R.
Almeida J.P.
Ambrose K.D.
Anderson F.
Andrew R.W.
Ashwell R.I.S.
Aubin K.
Babbage A.K.
Bagguley C.L.
Bailey J.
Beasley H.
Bethel G.
Bird C.P.
Bray-Allen S.
Brown J.Y.
Brown A.J.
Buckley D.
Burton J.
Bye J.
Carder C.
Chapman J.C.
Clark S.Y.
Clarke G.
Clee C.
Cobley V.
Collier R.E.
Corby N.
Coville G.J.
Davies J.
Deadman R.
Dunn M.
Earthrowl M.
Ellington A.G.
Errington H.
Frankish A.
Frankland J.
French L.
Garner P.
Garnett J.
Gay L.
Ghori M.R.J.
Gibson R.
Gilby L.M.
Gillett W.
Glithero R.J.
Grafham D.V.
Griffiths C.
Griffiths-Jones S.
Grocock R.
Hammond S.
Harrison E.S.I.
Hart E.
Haugen E.
Heath P.D.
Holmes S.
Holt K.
Howden P.J.
Hunt A.R.
Hunt S.E.
Hunter G.
Isherwood J.
James R.
Johnson C.
Johnson D.
Joy A.
Kay M.
Kershaw J.K.
Kibukawa M.
Kimberley A.M.
King A.
Knights A.J.
Lad H.
Laird G.
Lawlor S.
Leongamornlert D.A.
Lloyd D.M.
Loveland J.
Lovell J.
Lush M.J.
Lyne R.
Martin S.
Mashreghi-Mohammadi M.
Matthews L.
Matthews N.S.W.
McLaren S.
Milne S.
Mistry S.
Moore M.J.F.
Nickerson T.
O'Dell C.N.
Oliver K.
Palmeiri A.
Palmer S.A.
Parker A.
Patel D.
Pearce A.V.
Peck A.I.
Pelan S.
Phelps K.
Phillimore B.J.
Plumb R.
Rajan J.
Raymond C.
Rouse G.
Saenphimmachak C.
Sehra H.K.
Sheridan E.
Shownkeen R.
Sims S.
Skuce C.D.
Smith M.
Steward C.
Subramanian S.
Sycamore N.
Tracey A.
Tromans A.
Van Helmond Z.
Wall M.
Wallis J.M.
White S.
Whitehead S.L.
Wilkinson J.E.
Willey D.L.
Williams H.
Wilming L.
Wray P.W.
Wu Z.
Coulson A.
Vaudin M.
Sulston J.E.
Durbin R.M.
Hubbard T.
Wooster R.
Dunham I.
Carter N.P.
McVean G.
Ross M.T.
Harrow J.
Olson M.V.
Beck S.
Rogers J.
Bentley D.R.

title: The DNA sequence and biological annotation of human chromosome 1.

authors:
Mural R.J.
Istrail S.
Sutton G.G.
Florea L.
Halpern A.L.
Mobarry C.M.
Lippert R.
Walenz B.
Shatkay H.
Dew I.
Miller J.R.
Flanigan M.J.
Edwards N.J.
Bolanos R.
Fasulo D.
Halldorsson B.V.
Hannenhalli S.
Turner R.
Yooseph S.
Lu F.
Nusskern D.R.
Shue B.C.
Zheng X.H.
Zhong F.
Delcher A.L.
Huson D.H.
Kravitz S.A.
Mouchard L.
Reinert K.
Remington K.A.
Clark A.G.
Waterman M.S.
Eichler E.E.
Adams M.D.
Hunkapiller M.W.
Myers E.W.
Venter J.C.

title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)

authors:
Ota T.
Suzuki Y.
Nishikawa T.
Otsuki T.
Sugiyama T.
Irie R.
Wakamatsu A.
Hayashi K.
Sato H.
Nagai K.
Kimura K.
Makita H.
Sekine M.
Obayashi M.
Nishi T.
Shibahara T.
Tanaka T.
Ishii S.
Yamamoto J.
Saito K.
Kawai Y.
Isono Y.
Nakamura Y.
Nagahari K.
Murakami K.
Yasuda T.
Iwayanagi T.
Wagatsuma M.
Shiratori A.
Sudo H.
Hosoiri T.
Kaku Y.
Kodaira H.
Kondo H.
Sugawara M.
Takahashi M.
Kanda K.
Yokoi T.
Furuya T.
Kikkawa E.
Omura Y.
Abe K.
Kamihara K.
Katsuta N.
Sato K.
Tanikawa M.
Yamazaki M.
Ninomiya K.
Ishibashi T.
Yamashita H.
Murakawa K.
Fujimori K.
Tanai H.
Kimata M.
Watanabe M.
Hiraoka S.
Chiba Y.
Ishida S.
Ono Y.
Takiguchi S.
Watanabe S.
Yosida M.
Hotuta T.
Kusano J.
Kanehori K.
Takahashi-Fujii A.
Hara H.
Tanase T.-O.
Nomura Y.
Togiya S.
Komai F.
Hara R.
Takeuchi K.
Arita M.
Imose N.
Musashino K.
Yuuki H.
Oshima A.
Sasaki N.
Aotsuka S.
Yoshikawa Y.
Matsunawa H.
Ichihara T.
Shiohata N.
Sano S.
Moriya S.
Momiyama H.
Satoh N.
Takami S.
Terashima Y.
Suzuki O.
Nakagawa S.
Senoh A.
Mizoguchi H.
Goto Y.
Shimizu F.
Wakebe H.
Hishigaki H.
Watanabe T.
Sugiyama A.
Takemoto M.
Kawakami B.
Yamazaki M.
Watanabe K.
Kumagai A.
Itakura S.
Fukuzumi Y.
Fujimori Y.
Komiyama M.
Tashiro H.
Tanigami A.
Fujiwara T.
Ono T.
Yamada K.
Fujii Y.
Ozaki K.
Hirao M.
Ohmori Y.
Kawabata A.
Hikiji T.
Kobatake N.
Inagaki H.
Ikema Y.
Okamoto S.
Okitani R.
Kawakami T.
Noguchi S.
Itoh T.
Shigeta K.
Senba T.
Matsumura K.
Nakajima Y.
Mizuno T.
Morinaga M.
Sasaki M.
Togashi T.
Oyama M.
Hata H.
Watanabe M.
Komatsu T.
Mizushima-Sugano J.
Satoh T.
Shirai Y.
Takahashi Y.
Nakagawa K.
Okumura K.
Nagase T.
Nomura N.
Kikuchi H.
Masuho Y.
Yamashita R.
Nakai K.
Yada T.
Nakamura Y.
Ohara O.
Isogai T.
Sugano S.

title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 160-524 (ISOFORM 2)

authors:
Head B.
Griparic L.
Amiri M.
Gandre-Babbe S.
van der Bliek A.M.

title: Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells.

referencePositions:
FUNCTION
SUBCELLULAR LOCATION
PROTEOLYTIC PROCESSING
MUTAGENESIS OF HIS-331

title: Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis.

authors:
Desmurs M.
Foti M.
Raemy E.
Vaz F.M.
Martinou J.C.
Bairoch A.
Lane L.

title: C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1 complex assembly and supercomplex stabilization.

authors:
Rainbolt T.K.
Lebeau J.
Puchades C.
Wiseman R.L.

title: Reciprocal Degradation of YME1L and OMA1 Adapts Mitochondrial Proteolytic Activity during Stress.

authors:
Vaca Jacome A.S.
Rabilloud T.
Schaeffer-Reiss C.
Rompais M.
Ayoub D.
Lane L.
Bairoch A.
Van Dorsselaer A.
Carapito C.

title: N-terminome analysis of the human mitochondrial proteome.

authors:
Consolato F.
Maltecca F.
Tulli S.
Sambri I.
Casari G.

title: m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

authors:
Bohovych I.
Dietz J.V.
Swenson S.
Zahayko N.
Khalimonchuk O.

title: Redox regulation of the mitochondrial quality control protease Oma1.

authors:
Sekine S.
Wang C.
Sideris D.P.
Bunker E.
Zhang Z.
Youle R.J.

title: Reciprocal roles of Tom7 and OMA1 during mitochondrial import and activation of PINK1.

authors:
Fessler E.
Eckl E.M.
Schmitt S.
Mancilla I.A.
Meyer-Bender M.F.
Hanf M.
Philippou-Massier J.
Krebs S.
Zischka H.
Jae L.T.

title: A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol.

referencePositions:
FUNCTION
CATALYTIC ACTIVITY
ACTIVE SITE
MUTAGENESIS OF GLU-328

authors:
Guo X.
Aviles G.
Liu Y.
Tian R.
Unger B.A.
Lin Y.T.
Wiita A.P.
Xu K.
Correia M.A.
Kampmann M.

title: Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway.

referencePositions:
FUNCTION
CATALYTIC ACTIVITY
SUBCELLULAR LOCATION

authors:
Ge Y.
Shi X.
Boopathy S.
McDonald J.
Smith A.W.
Chao L.H.

title: Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane.

authors:
Daoud H.
Valdmanis P.N.
Gros-Louis F.
Belzil V.
Spiegelman D.
Henrion E.
Diallo O.
Desjarlais A.
Gauthier J.
Camu W.
Dion P.A.
Rouleau G.A.

title: Resequencing of 29 candidate genes in patients with familial and sporadic amyotrophic lateral sclerosis.

referencePositions: VARIANTS TYR-69; LEU-117; GLY-272; LEU-329 AND TYR-365

value: the mitochondrial metalloendopeptidase oma1 (oma1) family

value: 3 GO annotations based on evolutionary models

value: Cellular response to mitochondrial stress

value: Expressed in bronchial epithelial cell and 184 other cell types or tissues

value: P:mitochondrial respiratory chain complex assembly

value: P:negative regulation of mitochondrial fusion

value: P:positive regulation of apoptotic process

value: P:positive regulation of cold-induced thermogenesis

value: P:protein quality control for misfolded or incompletely synthesized proteins

value: metalloendopeptidase OMA1, mitochondrial isoform X1

value: Metalloproteases ('zincins'), catalytic domain


value: Myotubularin-related protein 9

value: Inactive phosphatidylinositol 3-phosphatase 9

value: Acts as an adapter for myotubularin-related phosphatases (PubMed:19038970, PubMed:22647598). Increases lipid phosphatase MTMR6 catalytic activity, specifically towards phosphatidylinositol 3,5-bisphosphate and MTMR6 binding affinity for phosphorylated phosphatidylinositols (PubMed:19038970, PubMed:22647598). Positively regulates lipid phosphatase MTMR7 catalytic activity (By similarity). Increases MTMR8 catalytic activity towards phosphatidylinositol 3-phosphate (PubMed:22647598). The formation of the MTMR6-MTMR9 complex, stabilizes both MTMR6 and MTMR9 protein levels (PubMed:19038970). Stabilizes MTMR8 protein levels (PubMed:22647598). Plays a role in the late stages of macropinocytosis possibly by regulating MTMR6-mediated dephosphorylation of phosphatidylinositol 3-phosphate in membrane ruffles (PubMed:24591580). Negatively regulates autophagy, in part via its association with MTMR8 (PubMed:22647598). Negatively regulates DNA damage-induced apoptosis, in part via its association with MTMR6 (PubMed:19038970, PubMed:22647598). Does not bind mono-, di- and tri-phosphorylated phosphatidylinositols, phosphatidic acid and phosphatidylserine (PubMed:19038970)

value: Homodimer (PubMed:19038970). Heterodimer (via C-terminus) with lipid phosphatase MTMR6 (via C-terminus) (PubMed:12890864, PubMed:16787938, PubMed:19038970, PubMed:23188820). Heterodimer (via coiled coil domain) with lipid phosphatase MTMR7 (via C-terminus) (By similarity). Heterodimer with lipid phosphatase MTMR8 (PubMed:16787938, PubMed:22647598)

commentType: INTERACTION

geneName: MOS

geneName: NMI

value: Localizes to ruffles during EGF-induced macropinocytosis (By similarity). Colocalizes with MTMR6 to the perinuclear region (PubMed:19038970). Partially localizes to the endoplasmic reticulum (PubMed:19038970)

value: Cytoplasm

value: Cell projection, ruffle membrane

value: Peripheral membrane protein

value: Cytoplasmic side

value: Cytoplasm, perinuclear region

value: Endoplasmic reticulum

value: Expressed in many tissues

value: The GRAM domain is required for cell membrane localization

value: The coiled coil domain mediates interaction with MTMR9

value: Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily

value: Although it belongs to the non-receptor class myotubularin subfamily, lacks the conserved active site cysteine residue at position 333 in the dsPTPase catalytic loop, suggesting that it has no phosphatase activity

description: Myotubularin-related protein 9

type: Domain

description: GRAM

description: Myotubularin phosphatase

type: Coiled coil

type: Modified residue

description: N-acetylmethionine

description: Phosphoserine

type: Alternative sequence

description: in isoform 2

type: Natural variant

description: found in a patient with global developmental delay, spasticity and epilepsy; uncertain significance

originalSequence: N

type: Sequence conflict

description: in Ref. 2; BAA91170

originalSequence: K

description: in Ref. 4; AAH22003

originalSequence: Q

Alternative splicing

category: Coding sequence diversity

Cell membrane

category: Cellular component

Coiled coil

category: Domain

Endocytosis

category: Biological process

authors:
Appel S.
Reichwald K.
Zimmermann W.
Reis A.
Rosenthal A.
Hennies H.C.

title: Identification and localization of a new human myotubularin-related protein gene, MTMR8, on 8p22-p23.

referencePositions: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1)

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)

authors:
Nusbaum C.
Mikkelsen T.S.
Zody M.C.
Asakawa S.
Taudien S.
Garber M.
Kodira C.D.
Schueler M.G.
Shimizu A.
Whittaker C.A.
Chang J.L.
Cuomo C.A.
Dewar K.
FitzGerald M.G.
Yang X.
Allen N.R.
Anderson S.
Asakawa T.
Blechschmidt K.
Bloom T.
Borowsky M.L.
Butler J.
Cook A.
Corum B.
DeArellano K.
DeCaprio D.
Dooley K.T.
Dorris L. III
Engels R.
Gloeckner G.
Hafez N.
Hagopian D.S.
Hall J.L.
Ishikawa S.K.
Jaffe D.B.
Kamat A.
Kudoh J.
Lehmann R.
Lokitsang T.
Macdonald P.
Major J.E.
Matthews C.D.
Mauceli E.
Menzel U.
Mihalev A.H.
Minoshima S.
Murayama Y.
Naylor J.W.
Nicol R.
Nguyen C.
O'Leary S.B.
O'Neill K.
Parker S.C.J.
Polley A.
Raymond C.K.
Reichwald K.
Rodriguez J.
Sasaki T.
Schilhabel M.
Siddiqui R.
Smith C.L.
Sneddon T.P.
Talamas J.A.
Tenzin P.
Topham K.
Venkataraman V.
Wen G.
Yamazaki S.
Young S.K.
Zeng Q.
Zimmer A.R.
Rosenthal A.
Birren B.W.
Platzer M.
Shimizu N.
Lander E.S.

title: DNA sequence and analysis of human chromosome 8.

title: Characterization of myotubularin-related protein 7 and its binding partner, myotubularin-related protein 9.

title: Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosome related functions.

referencePositions:
INTERACTION WITH MTMR6 AND MTMR8
SUBCELLULAR LOCATION

authors:
Dephoure N.
Zhou C.
Villen J.
Beausoleil S.A.
Bakalarski C.E.
Elledge S.J.
Gygi S.P.

title: A quantitative atlas of mitotic phosphorylation.

referencePositions: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-548

authors:
Zou J.
Chang S.C.
Marjanovic J.
Majerus P.W.

title: MTMR9 increases MTMR6 enzyme activity, stability, and role in apoptosis.

referencePositions:
FUNCTION
INTERACTION WITH MTMR6
SUBUNIT
SUBCELLULAR LOCATION

authors:
Gauci S.
Helbig A.O.
Slijper M.
Krijgsveld J.
Heck A.J.
Mohammed S.

title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

authors:
Mayya V.
Lundgren D.H.
Hwang S.-I.
Rezaul K.
Wu L.
Eng J.K.
Rodionov V.
Han D.K.

title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

authors:
Olsen J.V.
Vermeulen M.
Santamaria A.
Kumar C.
Miller M.L.
Jensen L.J.
Gnad F.
Cox J.
Jensen T.S.
Nigg E.A.
Brunak S.
Mann M.

title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

authors:
Burkard T.R.
Planyavsky M.
Kaupe I.
Breitwieser F.P.
Buerckstuemmer T.
Bennett K.L.
Superti-Furga G.
Colinge J.

title: Initial characterization of the human central proteome.

authors:
Zou J.
Zhang C.
Marjanovic J.
Kisseleva M.V.
Majerus P.W.
Wilson M.P.

title: Myotubularin-related protein (MTMR) 9 determines the enzymatic activity, substrate specificity, and role in autophagy of MTMR8.

authors:
Rigbolt K.T.
Prokhorova T.A.
Akimov V.
Henningsen J.
Johansen P.T.
Kratchmarova I.
Kassem M.
Mann M.
Olsen J.V.
Blagoev B.

title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

authors:
Mochizuki Y.
Ohashi R.
Kawamura T.
Iwanari H.
Kodama T.
Naito M.
Hamakubo T.

title: Phosphatidylinositol 3-phosphatase myotubularin-related protein 6 (MTMR6) is regulated by small GTPase Rab1B in the early secretory and autophagic pathways.

referencePositions:
INTERACTION WITH MTMR6
IDENTIFICATION BY MASS SPECTROMETRY

authors:
Bienvenut W.V.
Sumpton D.
Martinez A.
Lilla S.
Espagne C.
Meinnel T.
Giglione C.

title: Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.

referencePositions: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1

authors:
Van Damme P.
Lasa M.
Polevoda B.
Gazquez C.
Elosegui-Artola A.
Kim D.S.
De Juan-Pardo E.
Demeyer K.
Hole K.
Larrea E.
Timmerman E.
Prieto J.
Arnesen T.
Sherman F.
Gevaert K.
Aldabe R.

title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

authors:
Zhou H.
Di Palma S.
Preisinger C.
Peng M.
Polat A.N.
Heck A.J.
Mohammed S.

title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

authors:
Maekawa M.
Terasaka S.
Mochizuki Y.
Kawai K.
Ikeda Y.
Araki N.
Skolnik E.Y.
Taguchi T.
Arai H.

title: Sequential breakdown of 3-phosphorylated phosphoinositides is essential for the completion of macropinocytosis.

authors:
Maddirevula S.
Alzahrani F.
Al-Owain M.
Al Muhaizea M.A.
Kayyali H.R.
AlHashem A.
Rahbeeni Z.
Al-Otaibi M.
Alzaidan H.I.
Balobaid A.
El Khashab H.Y.
Bubshait D.K.
Faden M.
Yamani S.A.
Dabbagh O.
Al-Mureikhi M.
Jasser A.A.
Alsaif H.S.
Alluhaydan I.
Seidahmed M.Z.
Alabbasi B.H.
Almogarri I.
Kurdi W.
Akleh H.
Qari A.
Al Tala S.M.
Alhomaidi S.
Kentab A.Y.
Salih M.A.
Chedrawi A.
Alameer S.
Tabarki B.
Shamseldin H.E.
Patel N.
Ibrahim N.
Abdulwahab F.
Samira M.
Goljan E.
Abouelhoda M.
Meyer B.F.
Hashem M.
Shaheen R.
AlShahwan S.
Alfadhel M.
Ben-Omran T.
Al-Qattan M.M.
Monies D.
Alkuraya F.S.

title: Autozygome and high throughput confirmation of disease genes candidacy.

value: 4 GO annotations based on evolutionary models

value: Synthesis of PIPs at the plasma membrane

value: Synthesis of PIPs at the late endosome membrane

value: Synthesis of IP2, IP, and Ins in the cytosol

value: Expressed in endothelial cell and 209 other cell types or tissues

value: P:positive regulation of phosphatase activity

value: P:regulation of phosphatidylinositol dephosphorylation

value: Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)

value: (Phosphotyrosine protein) phosphatases II


value: Myosin regulatory light chain 10

value: Myosin light chain 2, lymphocyte-specific

value: Precursor lymphocyte-specific regulatory light chain

value: PLRLC

value: Myosin is a hexamer of 2 heavy chains and 4 light chains

value: This chain binds calcium

commentType: MISCELLANEOUS

description: Myosin regulatory light chain 10

description: EF-hand 1

description: EF-hand 2

description: EF-hand 3

description: in dbSNP:rs12216595

database: dbSNP

originalSequence: M

Proteomics identification

category: Technical term

citationType: submission

authors:
Mural R.J.
Istrail S.
Sutton G.G.
Florea L.
Halpern A.L.
Mobarry C.M.
Lippert R.
Walenz B.
Shatkay H.
Dew I.
Miller J.R.
Flanigan M.J.
Edwards N.J.
Bolanos R.
Fasulo D.
Halldorsson B.V.
Hannenhalli S.
Turner R.
Yooseph S.
Lu F.
Nusskern D.R.
Shue B.C.
Zheng X.H.
Zhong F.
Delcher A.L.
Huson D.H.
Kravitz S.A.
Mouchard L.
Reinert K.
Remington K.A.
Clark A.G.
Waterman M.S.
Eichler E.E.
Adams M.D.
Hunkapiller M.W.
Myers E.W.
Venter J.C.

submissionDatabase: EMBL/GenBank/DDBJ databases

citationType: journal article

database: PubMed

database: DOI

title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

journal: Genome Res.

value: Skin

type: TISSUE

database: EMBL

key: ProteinId

key: Status

key: MoleculeType

value: mRNA

database: CCDS

key: Description

database: RefSeq

key: NucleotideSequenceId

database: AlphaFoldDB

database: SMR

database: BioGRID

key: Interactions

database: FunCoup

key: Number of interactors

database: IntAct

database: NDEx

key: Evidences

value: 1 NDEx IQuery Curated Pathway

database: STRING

database: iPTMnet

database: PhosphoSitePlus

database: BioMuta

database: DMDM

database: jPOST

value: 3 GO annotations based on evolutionary models

value: Expressed in olfactory bulb and 155 other cell types or tissues

value: Myosin regulatory light chain 2, atrial isoform

value: Putative myosin regulatory light chain sqh


value: Glycerol-3-phosphate acyltransferase 1, mitochondrial

value: GPAM

value: Mitochondrial membrane protein that catalyzes the essential first step of biosynthesis of glycerolipids such as triglycerides, phosphatidic acids and lysophosphatidic acids (PubMed:18238778, PubMed:19075029, PubMed:36522428). Esterifies acyl-group from acyl-coenzyme A (acyl-CoA) to the sn-1 position of glycerol-3-phosphate, to produce lysophosphatidic acid (PubMed:18238778). Has a narrow hydrophobic binding cleft that selects for a linear acyl chain (PubMed:36522428). Catalytic activity is higher for substrates with a 16-carbon acyl chain (PubMed:36522428)

name: sn-glycerol 3-phosphate + an acyl-CoA = a 1-acyl-sn-glycero-3-phosphate + CoA

database: Rhea

database: ChEBI

directionType: left-to-right

name: (9Z,12Z)-octadecadienoyl-CoA + sn-glycerol 3-phosphate = 1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + CoA

name: sn-glycerol 3-phosphate + (9Z)-octadecenoyl-CoA = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA

name: sn-glycerol 3-phosphate + octadecanoyl-CoA = 1-octadecanoyl-sn-glycero-3-phosphate + CoA

name: sn-glycerol 3-phosphate + hexadecanoyl-CoA = 1-hexadecanoyl-sn-glycero-3-phosphate + CoA

name: dodecanoyl-CoA + sn-glycerol 3-phosphate = 1-dodecanoyl-sn-glycerol 3-phosphate + CoA

name: 1-acyl-sn-glycero-3-phospho-(1'-sn-glycerol) + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) + CoA

value: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-diacylglycerol from sn-glycerol 3-phosphate: step 1/3

commentType: PATHWAY

geneName: CIDEB

value: Associated with the mitochondrion outer membrane of hepatic cells via a patch of basic residues

value: Mitochondrion outer membrane

value: Peripheral membrane protein

value: The HXXXXD motif is essential for acyltransferase activity and contributes to the binding of the cysteamine moiety of the acyl-CoA and the phosphate moiety of the glycerol-3-phosphate

description: Cytoplasmic

description: Cytoplasmic

description: Important for mitochondrial localization

description: Disordered

description: HXXXXD motif

description: Basic and acidic residues

description: Phosphoserine

description: Phosphoserine

description: Phosphoserine

description: in dbSNP:rs11549703

description: in dbSNP:rs2792751

description: in dbSNP:rs10787428

description: in dbSNP:rs35019520

description: Abrogates mitochondrial localization; when associated with E-98, E-100, E-101, E-102, E-107, E-108 and E-118.

description: Abrogates mitochondrial localization; when associated with E-89, E-100, E-101, E-102, E-107, E-108 and E-118.

description: Abrogates mitochondrial localization; when associated with E-89, E-98, E-101, E-102, E-107, E-108 and E-118.

description: Abrogates mitochondrial localization; when associated with E-89, E-98, E-100, E-102, E-107, E-108 and E-118.

description: Abrogates mitochondrial localization; when associated with E-89, E-98, E-100, E-101, E-107, E-108 and E-118.

description: Abrogates mitochondrial localization; when associated with E-89, E-98, E-100, E-101, E-102, E-108 and E-118.

description: Abrogates mitochondrial localization; when associated with E-89, E-98, E-100, E-101, E-102, E-107 and E-118.

description: Abrogates mitochondrial localization; when associated with E-89, E-98, E-100, E-101, E-102, E-107 and E-108.

description: Abolishes catalytic activity.

description: Abolishes catalytic activity.

description: Abolishes catalytic activity.

description: Abolishes catalytic activity.

description: Abolishes catalytic activity.

description: Abolishes catalytic activity.

description: Impairs catalytic activity.

description: in Ref. 1; CAD89932

description: in Ref. 1; CAD89932

authors:
Bechtel S.
Rosenfelder H.
Duda A.
Schmidt C.P.
Ernst U.
Wellenreuther R.
Mehrle A.
Schuster C.
Bahr A.
Bloecker H.
Heubner D.
Hoerlein A.
Michel G.
Wedler H.
Koehrer K.
Ottenwaelder B.
Poustka A.
Wiemann S.
Schupp I.

title: The full-ORF clone resource of the German cDNA consortium.

authors:
Deloukas P.
Earthrowl M.E.
Grafham D.V.
Rubenfield M.
French L.
Steward C.A.
Sims S.K.
Jones M.C.
Searle S.
Scott C.
Howe K.
Hunt S.E.
Andrews T.D.
Gilbert J.G.R.
Swarbreck D.
Ashurst J.L.
Taylor A.
Battles J.
Bird C.P.
Ainscough R.
Almeida J.P.
Ashwell R.I.S.
Ambrose K.D.
Babbage A.K.
Bagguley C.L.
Bailey J.
Banerjee R.
Bates K.
Beasley H.
Bray-Allen S.
Brown A.J.
Brown J.Y.
Burford D.C.
Burrill W.
Burton J.
Cahill P.
Camire D.
Carter N.P.
Chapman J.C.
Clark S.Y.
Clarke G.
Clee C.M.
Clegg S.
Corby N.
Coulson A.
Dhami P.
Dutta I.
Dunn M.
Faulkner L.
Frankish A.
Frankland J.A.
Garner P.
Garnett J.
Gribble S.
Griffiths C.
Grocock R.
Gustafson E.
Hammond S.
Harley J.L.
Hart E.
Heath P.D.
Ho T.P.
Hopkins B.
Horne J.
Howden P.J.
Huckle E.
Hynds C.
Johnson C.
Johnson D.
Kana A.
Kay M.
Kimberley A.M.
Kershaw J.K.
Kokkinaki M.
Laird G.K.
Lawlor S.
Lee H.M.
Leongamornlert D.A.
Laird G.
Lloyd C.
Lloyd D.M.
Loveland J.
Lovell J.
McLaren S.
McLay K.E.
McMurray A.
Mashreghi-Mohammadi M.
Matthews L.
Milne S.
Nickerson T.
Nguyen M.
Overton-Larty E.
Palmer S.A.
Pearce A.V.
Peck A.I.
Pelan S.
Phillimore B.
Porter K.
Rice C.M.
Rogosin A.
Ross M.T.
Sarafidou T.
Sehra H.K.
Shownkeen R.
Skuce C.D.
Smith M.
Standring L.
Sycamore N.
Tester J.
Thorpe A.
Torcasso W.
Tracey A.
Tromans A.
Tsolas J.
Wall M.
Walsh J.
Wang H.
Weinstock K.
West A.P.
Willey D.L.
Whitehead S.L.
Wilming L.
Wray P.W.
Young L.
Chen Y.
Lovering R.C.
Moschonas N.K.
Siebert R.
Fechtel K.
Bentley D.
Durbin R.M.
Hubbard T.
Doucette-Stamm L.
Beck S.
Smith D.R.
Rogers J.

title: The DNA sequence and comparative analysis of human chromosome 10.

authors:
Nagase T.
Kikuno R.
Nakayama M.
Hirosawa M.
Ohara O.

title: Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 167-828

authors:
Olsen J.V.
Blagoev B.
Gnad F.
Macek B.
Kumar C.
Mortensen P.
Mann M.

title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

referencePositions: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]

authors:
Chen Y.Q.
Kuo M.-S.
Li S.
Bui H.H.
Peake D.A.
Sanders P.E.
Thibodeaux S.J.
Chu S.
Qian Y.-W.
Zhao Y.
Bredt D.S.
Moller D.E.
Konrad R.J.
Beigneux A.P.
Young S.G.
Cao G.

title: AGPAT6 is a novel microsomal glycerol-3-phosphate acyltransferase.

authors:
Han G.
Ye M.
Zhou H.
Jiang X.
Feng S.
Jiang X.
Tian R.
Wan D.
Zou H.
Gu J.

title: Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography.

referencePositions: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695

authors:
Zhao Y.
Chen Y.-Q.
Li S.
Konrad R.J.
Cao G.

title: The microsomal cardiolipin remodeling enzyme acyl-CoA lysocardiolipin acyltransferase is an acyltransferase of multiple anionic lysophospholipids.

authors:
Bian Y.
Song C.
Cheng K.
Dong M.
Wang F.
Huang J.
Sun D.
Wang L.
Ye M.
Zou H.

title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

authors:
Johnson Z.L.
Ammirati M.
Wasilko D.J.
Chang J.S.
Noell S.
Foley T.L.
Yoon H.
Smith K.
Asano S.
Hales K.
Wan M.
Yang Q.
Piotrowski M.A.
Farley K.A.
Gilbert T.
Aschenbrenner L.M.
Fennell K.F.
Dutra J.K.
Xu M.
Guo C.
Varghese A.E.
Bellenger J.
Quinn A.
Am Ende C.W.
West G.M.
Griffor M.C.
Bennett D.
Calabrese M.
Steppan C.M.
Han S.
Wu H.

title: Structural basis of the acyl-transfer mechanism of human GPAT1.

referencePositions: STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 80-828

value: 4 GO annotations based on evolutionary models

value: Activation of gene expression by SREBF (SREBP)

value: RUNX1 regulates estrogen receptor mediated transcription

value: MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis

value: Expressed in pericardium and 181 other cell types or tissues

value: P:phosphatidic acid biosynthetic process

value: GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 1, MITOCHONDRIAL


scientificName: Schizosaccharomyces pombe (strain 972 / ATCC 24843)

commonName: Fission yeast

lineage: Eukaryota Fungi Dikarya Ascomycota Taphrinomycotina Schizosaccharomycetes Schizosaccharomycetales Schizosaccharomycetaceae Schizosaccharomyces

value: Probable zinc transporter cis4

value: Probable zinc transporter involved in Golgi membrane trafficking through the regulation of zinc homeostasis

commentType: FUNCTION

value: Interacts with zrg17

value: Endoplasmic reticulum membrane

value: Multi-pass membrane protein

value: Golgi apparatus, cis-Golgi network membrane

value: Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily

type: Chain

description: Probable zinc transporter cis4

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Helical

description: Disordered

source: SAM

type: Mutagenesis

description: In cis4-1; confers sensitivities to the calcineurin inhibitor FK506 and to a high concentration of MgCl2.

originalSequence: G

description: In cis4-2; confers sensitivities to the calcineurin inhibitor FK506 and to a high concentration of MgCl2.

description: in Ref. 2; BAA13900

originalSequence: L

description: in Ref. 2; BAA13900

description: in Ref. 2; BAA13900

originalSequence: I

authors:
Wood V.
Gwilliam R.
Rajandream M.A.
Lyne M.H.
Lyne R.
Stewart A.
Sgouros J.G.
Peat N.
Hayles J.
Baker S.G.
Basham D.
Bowman S.
Brooks K.
Brown D.
Brown S.
Chillingworth T.
Churcher C.M.
Collins M.
Connor R.
Cronin A.
Davis P.
Feltwell T.
Fraser A.
Gentles S.
Goble A.
Hamlin N.
Harris D.E.
Hidalgo J.
Hodgson G.
Holroyd S.
Hornsby T.
Howarth S.
Huckle E.J.
Hunt S.
Jagels K.
James K.D.
Jones L.
Jones M.
Leather S.
McDonald S.
McLean J.
Mooney P.
Moule S.
Mungall K.L.
Murphy L.D.
Niblett D.
Odell C.
Oliver K.
O'Neil S.
Pearson D.
Quail M.A.
Rabbinowitsch E.
Rutherford K.M.
Rutter S.
Saunders D.
Seeger K.
Sharp S.
Skelton J.
Simmonds M.N.
Squares R.
Squares S.
Stevens K.
Taylor K.
Taylor R.G.
Tivey A.
Walsh S.V.
Warren T.
Whitehead S.
Woodward J.R.
Volckaert G.
Aert R.
Robben J.
Grymonprez B.
Weltjens I.
Vanstreels E.
Rieger M.
Schaefer M.
Mueller-Auer S.
Gabel C.
Fuchs M.
Duesterhoeft A.
Fritzc C.
Holzer E.
Moestl D.
Hilbert H.
Borzym K.
Langer I.
Beck A.
Lehrach H.
Reinhardt R.
Pohl T.M.
Eger P.
Zimmermann W.
Wedler H.
Wambutt R.
Purnelle B.
Goffeau A.
Cadieu E.
Dreano S.
Gloux S.
Lelaure V.
Mottier S.
Galibert F.
Aves S.J.
Xiang Z.
Hunt C.
Moore K.
Hurst S.M.
Lucas M.
Rochet M.
Gaillardin C.
Tallada V.A.
Garzon A.
Thode G.
Daga R.R.
Cruzado L.
Jimenez J.
Sanchez M.
del Rey F.
Benito J.
Dominguez A.
Revuelta J.L.
Moreno S.
Armstrong J.
Forsburg S.L.
Cerutti L.
Lowe T.
McCombie W.R.
Paulsen I.
Potashkin J.
Shpakovski G.V.
Ussery D.
Barrell B.G.
Nurse P.

database: PubMed

database: DOI

title: The genome sequence of Schizosaccharomyces pombe.

journal: Nature

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]

type: STRAIN

authors:
Yoshioka S.
Kato K.
Nakai K.
Okayama H.
Nojima H.

title: Identification of open reading frames in Schizosaccharomyces pombe cDNAs.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 377-732

authors:
Matsuyama A.
Arai R.
Yashiroda Y.
Shirai A.
Kamata A.
Sekido S.
Kobayashi Y.
Hashimoto A.
Hamamoto M.
Hiraoka Y.
Horinouchi S.
Yoshida M.

title: ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.

referencePositions: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]

authors:
Fang Y.
Sugiura R.
Ma Y.
Yada-Matsushima T.
Umeno H.
Kuno T.

title: Cation diffusion facilitator Cis4 is implicated in Golgi membrane trafficking via regulating zinc homeostasis in fission yeast.

referencePositions:
FUNCTION
MUTAGENESIS OF GLY-375 AND GLY-393
SUBCELLULAR LOCATION
INTERACTION WITH ZRG17

value: Zinc efflux and compartmentalization by the SLC30 family

value: F:zinc ion transmembrane transporter activity

value: Cation efflux protein transmembrane domain-like


entryType: UniProtKB unreviewed (TrEMBL)

scientificName: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)

source: EMBL

source: Proteomes

lineage:
Bacteria
Bacillati
Actinomycetota
Actinomycetes
Kitasatosporales
Streptomycetaceae
Streptomyces
Streptomyces albidoflavus group

proteinExistence: 4: Predicted

value: RNA polymerase sigma factor

description: Disordered

authors:
Redenbach M.
Kieser H.M.
Denapaite D.
Eichner A.
Cullum J.
Kinashi H.
Hopwood D.A.

title: A set of ordered cosmids and a detailed genetic and physical map for the 8 Mb Streptomyces coelicolor A3(2) chromosome.

journal: Mol. Microbiol.

authors:
Bentley S.D.
Chater K.F.
Cerdeno-Tarraga A.M.
Challis G.L.
Thomson N.R.
James K.D.
Harris D.E.
Quail M.A.
Kieser H.
Harper D.
Bateman A.
Brown S.
Chandra G.
Chen C.W.
Collins M.
Cronin A.
Fraser A.
Goble A.
Hidalgo J.
Hornsby T.
Howarth S.
Huang C.H.
Kieser T.
Larke L.
Murphy L.
Oliver K.
O'Neil S.
Rabbinowitsch E.
Rajandream M.A.
Rutherford K.
Rutter S.
Seeger K.
Saunders D.
Sharp S.
Squares R.
Squares S.
Taylor K.
Warren T.
Wietzorrek A.
Woodward J.
Barrell B.G.
Parkhill J.
Hopwood D.A.

title: Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

database: EMBL

database: RefSeq

database: PaxDb

database: GeneID

database: KEGG

database: PATRIC

key: GeneDesignation

database: eggNOG

key: ToxonomicScope

value: Bacteria

database: HOGENOM

database: InParanoid

database: OrthoDB

database: PhylomeDB

database: Proteomes

key: Component

value: Chromosome

database: GO

key: GoTerm

value: F:sigma factor activity

key: GoEvidenceType

key: EntryName

value: Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain

key: MatchStatus

database: InterPro

database: PANTHER

value: ECF RNA POLYMERASE SIGMA FACTOR SIGI-RELATED

value: SIGMA 19 FACTOR

database: SUPFAM

value: Sigma3 and sigma4 domains of RNA polymerase sigma factors


source: Google

value: Secreted protein

database: PubMed

database: DOI

database: AlphaFoldDB

database: STRING

database: AbasyAtlas

database: Pfam


value: Dual oxidase 1

value: Large NOX 1

value: Long NOX 1

value: NADPH thyroid oxidase 1

value: Thyroid oxidase 1

value: DUOX

value: Generates hydrogen peroxide (H2O2) which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO (PubMed:10806195, PubMed:15972824). Plays a role in thyroid hormone synthesis (PubMed:10806195). Also required for lactoperoxidase-mediated antimicrobial defense at the surface of mucosa (PubMed:12824283). Antimicrobial agent hypothiocyanite (OSCN-), which is produced by LPO from DUOX1-derived H2O2, promotes influenza virus inactivation by reducing viral binding to and entry into host cells (PubMed:34168077). Promotes antiviral immunity by increasing airway cytokine levels, promoting innate immune cell recruitment and reducing airway epithelial cell apoptosis (By similarity). In response to bacterial stimuli, activated by ATP and promotes EGFR/ERK signaling, ADAM17 activation, and EGFR ligand shedding, leading to enhanced CXCL8/IL8 expression and secretion in airway epithelia (PubMed:19386603). Synthesizes NAADP from its reduced NAADPH form which promotes Ca(2+) signaling during T cell activation (PubMed:34784249). In addition to its oxidase activity, has also been shown to have peroxidase activity through its N-terminal peroxidase-like domain (PubMed:11514595). However, another study showed that the isolated peroxidase-like domain does not bind heme and has no intrinsic peroxidase activity (PubMed:19460756)

NADH + O2 + H(+) = H2O2 + NAD(+)

database: Rhea

database: ChEBI

value: The NADPH oxidase activity is calcium-dependent (PubMed:11514595). It is activated by release of cellular ATP which is promoted by bacterial infection (PubMed:19386603). Peroxidase activity is inhibited by aminobenzohydrazide (PubMed:15972824)

value: Hormone biosynthesis; thyroid hormone biosynthesis

value: Heterotetramer with DUOXA1 consisting of 2 DUOX1-DUOXA1 heterodimers (PubMed:33420071). This may represent the inactive state (By similarity). Has also been detected as a heterodimer with DUOXA1 which has been proposed to be the active state (By similarity). Interacts with TXNDC11, TPO and CYBA (PubMed:15561711)

value: Localizes to the apical membrane of epithelial cells

value: Apical cell membrane

value: Expressed in thyrocytes and tracheal surface epithelial cells (at protein level). Expressed in thyroid, trachea, bronchium, and to a lower extent, in placenta, testis, prostate, pancreas and heart

value: Widely expressed in fetal tissues

commentType: DEVELOPMENTAL STAGE

value: By forskolin (at protein level). By thyrotropin and the Th2-specific cytokines IL-4 and IL-13

commentType: INDUCTION

value: N-glycosylated

value: In the N-terminal section; belongs to the peroxidase family

value: The role of the N-terminal peroxidase-like domain is unclear. The domain has been shown in one study to have peroxidase activity when expressed in E.coli (PubMed:11514595). However, another study showed that the isolated domain does not bind heme and has no intrinsic peroxidase activity (PubMed:19460756)

sequenceCautionType: Erroneous termination

note: Truncated C-terminus.

type: Signal

description: Dual oxidase 1

description: Extracellular

description: Helical

description: Cytoplasmic

description: Helical

description: Extracellular

description: Helical

description: Cytoplasmic

description: Helical

description: Extracellular

description: Helical

description: Cytoplasmic

description: Helical

description: Extracellular

description: Helical

description: Cytoplasmic

description: EF-hand 1

description: EF-hand 2

description: EF-hand 3

description: Ferric oxidoreductase

description: FAD-binding FR-type

description: Peroxidase-like

description: Disordered

description: Interaction with TXNDC11

description: axial binding residue

description: axial binding residue

description: axial binding residue

description: axial binding residue

description: N-linked (GlcNAc...) asparagine

description: N-linked (GlcNAc...) asparagine

description: N-linked (GlcNAc...) asparagine

description: N-linked (GlcNAc...) asparagine

description: N-linked (GlcNAc...) asparagine

description: in isoform 2

description: in isoform 2

description: in dbSNP:rs16939743

description: in dbSNP:rs16939752

description: in dbSNP:rs2458236

description: Severely reduces tetramer formation.

description: Fails to assemble with DUOXA1; when associated with A-174.

description: Fails to assemble with DUOXA1; when associated with A-109.

description: Fails to assemble with DUOXA1; when associated with A-397.

description: Fails to assemble with DUOXA1; when associated with A-332.

description: Severely reduces tetramer formation.

description: in Ref. 3; AK128591

description: in Ref. 3; BAD18816

authors:
De Deken X.
Wang D.
Many M.-C.
Costagliola S.
Libert F.
Vassart G.
Dumont J.E.
Miot F.

title: Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
SUBCELLULAR LOCATION
TISSUE SPECIFICITY
INDUCTION

authors:
Edens W.A.
Sharling L.
Cheng G.
Shapira R.
Kinkade J.M.
Lee T.
Edens H.A.
Tang X.
Sullards C.
Flaherty D.B.
Benian G.M.
Lambeth J.D.

title: Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
VARIANT PHE-1178
FUNCTION
CATALYTIC ACTIVITY
ACTIVITY REGULATION
DEVELOPMENTAL STAGE
TISSUE SPECIFICITY

authors:
Ota T.
Suzuki Y.
Nishikawa T.
Otsuki T.
Sugiyama T.
Irie R.
Wakamatsu A.
Hayashi K.
Sato H.
Nagai K.
Kimura K.
Makita H.
Sekine M.
Obayashi M.
Nishi T.
Shibahara T.
Tanaka T.
Ishii S.
Yamamoto J.
Saito K.
Kawai Y.
Isono Y.
Nakamura Y.
Nagahari K.
Murakami K.
Yasuda T.
Iwayanagi T.
Wagatsuma M.
Shiratori A.
Sudo H.
Hosoiri T.
Kaku Y.
Kodaira H.
Kondo H.
Sugawara M.
Takahashi M.
Kanda K.
Yokoi T.
Furuya T.
Kikkawa E.
Omura Y.
Abe K.
Kamihara K.
Katsuta N.
Sato K.
Tanikawa M.
Yamazaki M.
Ninomiya K.
Ishibashi T.
Yamashita H.
Murakawa K.
Fujimori K.
Tanai H.
Kimata M.
Watanabe M.
Hiraoka S.
Chiba Y.
Ishida S.
Ono Y.
Takiguchi S.
Watanabe S.
Yosida M.
Hotuta T.
Kusano J.
Kanehori K.
Takahashi-Fujii A.
Hara H.
Tanase T.-O.
Nomura Y.
Togiya S.
Komai F.
Hara R.
Takeuchi K.
Arita M.
Imose N.
Musashino K.
Yuuki H.
Oshima A.
Sasaki N.
Aotsuka S.
Yoshikawa Y.
Matsunawa H.
Ichihara T.
Shiohata N.
Sano S.
Moriya S.
Momiyama H.
Satoh N.
Takami S.
Terashima Y.
Suzuki O.
Nakagawa S.
Senoh A.
Mizoguchi H.
Goto Y.
Shimizu F.
Wakebe H.
Hishigaki H.
Watanabe T.
Sugiyama A.
Takemoto M.
Kawakami B.
Yamazaki M.
Watanabe K.
Kumagai A.
Itakura S.
Fukuzumi Y.
Fujimori Y.
Komiyama M.
Tashiro H.
Tanigami A.
Fujiwara T.
Ono T.
Yamada K.
Fujii Y.
Ozaki K.
Hirao M.
Ohmori Y.
Kawabata A.
Hikiji T.
Kobatake N.
Inagaki H.
Ikema Y.
Okamoto S.
Okitani R.
Kawakami T.
Noguchi S.
Itoh T.
Shigeta K.
Senba T.
Matsumura K.
Nakajima Y.
Mizuno T.
Morinaga M.
Sasaki M.
Togashi T.
Oyama M.
Hata H.
Watanabe M.
Komatsu T.
Mizushima-Sugano J.
Satoh T.
Shirai Y.
Takahashi Y.
Nakagawa K.
Okumura K.
Nagase T.
Nomura N.
Kikuchi H.
Masuho Y.
Yamashita R.
Nakai K.
Yada T.
Nakamura Y.
Ohara O.
Isogai T.
Sugano S.

title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1030-1551 (ISOFORMS 1/2)

authors:
Zody M.C.
Garber M.
Sharpe T.
Young S.K.
Rowen L.
O'Neill K.
Whittaker C.A.
Kamal M.
Chang J.L.
Cuomo C.A.
Dewar K.
FitzGerald M.G.
Kodira C.D.
Madan A.
Qin S.
Yang X.
Abbasi N.
Abouelleil A.
Arachchi H.M.
Baradarani L.
Birditt B.
Bloom S.
Bloom T.
Borowsky M.L.
Burke J.
Butler J.
Cook A.
DeArellano K.
DeCaprio D.
Dorris L. III
Dors M.
Eichler E.E.
Engels R.
Fahey J.
Fleetwood P.
Friedman C.
Gearin G.
Hall J.L.
Hensley G.
Johnson E.
Jones C.
Kamat A.
Kaur A.
Locke D.P.
Madan A.
Munson G.
Jaffe D.B.
Lui A.
Macdonald P.
Mauceli E.
Naylor J.W.
Nesbitt R.
Nicol R.
O'Leary S.B.
Ratcliffe A.
Rounsley S.
She X.
Sneddon K.M.B.
Stewart S.
Sougnez C.
Stone S.M.
Topham K.
Vincent D.
Wang S.
Zimmer A.R.
Birren B.W.
Hood L.
Lander E.S.
Nusbaum C.

title: Analysis of the DNA sequence and duplication history of human chromosome 15.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)

title: Characterization of ThOX proteins as components of the thyroid H(2)O(2)-generating system.

authors:
Geiszt M.
Witta J.
Baffi J.
Lekstrom K.
Leto T.L.

title: Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense.

authors:
Schwarzer C.
Machen T.E.
Illek B.
Fischer H.

title: NADPH oxidase-dependent acid production in airway epithelial cells.

authors:
Harper R.W.
Xu C.
Eiserich J.P.
Chen Y.
Kao C.-Y.
Thai P.
Setiadi H.
Wu R.

title: Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium.

authors:
Wang D.
De Deken X.
Milenkovic M.
Song Y.
Pirson I.
Dumont J.E.
Miot F.

title: Identification of a novel partner of duox: EFP1, a thioredoxin-related protein.

authors:
Ameziane-El-Hassani R.
Morand S.
Boucher J.L.
Frapart Y.-M.
Apostolou D.
Agnandji D.
Gnidehou S.
Ohayon R.
Noel-Hudson M.-S.
Francon J.
Lalaoui K.
Virion A.
Dupuy C.

title: Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity.

authors:
Boots A.W.
Hristova M.
Kasahara D.I.
Haenen G.R.
Bast A.
van der Vliet A.

title: ATP-mediated activation of the NADPH oxidase DUOX1 mediates airway epithelial responses to bacterial stimuli.

title: Caenorhabditis elegans and human dual oxidase 1 (DUOX1) 'peroxidase' domains: insights into heme binding and catalytic activity.

authors:
Sarr D.
Gingerich A.D.
Asthiwi N.M.
Almutairi F.
Sautto G.A.
Ecker J.
Nagy T.
Kilgore M.B.
Chandler J.D.
Ross T.M.
Tripp R.A.
Rada B.

title: Dual oxidase 1 promotes antiviral innate immunity.

authors:
Gu F.
Krueger A.
Roggenkamp H.G.
Alpers R.
Lodygin D.
Jaquet V.
Moeckl F.
Hernandez L.C.
Winterberg K.
Bauche A.
Rosche A.
Grasberger H.
Kao J.Y.
Schetelig D.
Werner R.
Schroeder K.
Carty M.
Bowie A.G.
Huber S.
Meier C.
Mittruecker H.W.
Heeren J.
Krause K.H.
Fluegel A.
Diercks B.P.
Guse A.H.

title: Dual NADPH oxidases DUOX1 and DUOX2 synthesize NAADP and are necessary for Ca2+ signaling during T cell activation.

referencePositions:
FUNCTION
CATALYTIC ACTIVITY
SUBCELLULAR LOCATION

authors:
Kohda A.
Kamakura S.
Hayase J.
Sumimoto H.

title: The NADPH oxidases DUOX1 and DUOX2 are sorted to the apical plasma membrane in epithelial cells via their respective maturation factors DUOXA1 and DUOXA2.

referencePositions:
INTERACTION WITH DUOXA1
SUBCELLULAR LOCATION

title: Structures of human dual oxidase 1 complex in low-calcium and high-calcium states.

referencePositions: STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) IN COMPLEX WITH DUOXA1; CA(2+); FAD; NADPH AND HEME

referencePositions: GLYCOSYLATION AT ASN-94; ASN-342 AND ASN-534

referencePositions: MUTAGENESIS OF ARG-50; ASP-109; ASP-174; THR-332; ASP-397 AND ARG-507

value: the phagocyte (gp91(phox)) nadph oxidase family

value: Tissue enhanced (epididymis, esophagus, skin)

value: 6 GO annotations based on evolutionary models

value: Expressed in tongue squamous epithelium and 138 other cell types or tissues

value: F:superoxide-generating NAD(P)H oxidase activity

value: P:hydrogen peroxide biosynthetic process

value: P:positive regulation of defense response to bacterium

value: P:positive regulation of interleukin-8 production

value: P:regulation of thyroid hormone generation

value: Haem peroxidase domain superfamily, animal type

value: Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module

value: Ferredoxin reductase-like, C-terminal NADP-linked domain


source: HAMAP-Rule

value: NAD-dependent protein deacylase sirtuin-5, mitochondrial

value: Regulatory protein SIR2 homolog 5

value: SIR2-like protein 5

value: NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation (PubMed:29180469). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as UOX

commentType: CATALYTIC ACTIVITY

name: N(6)-malonyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-malonyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

name: N(6)-succinyl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-succinyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

name: N(6)-glutaryl-L-lysyl-[protein] + NAD(+) + H2O = 2''-O-glutaryl-ADP-D-ribose + nicotinamide + L-lysyl-[protein]

commentType: COFACTOR

value: Binds 1 zinc ion per subunit.

value: Inhibited by suramin. NAD-dependent lysine desuccinylase activity is inhibited by physiological nicotinamide concentrations, while deacetylase activity is not. In contrast, resveratrol activates deacetylase activity, while inhibiting desuccinylase activity

commentType: BIOPHYSICOCHEMICAL PROPERTIES

unit: uM

substrate: a synthetic histone H3K9 malonyllysine peptide

substrate: a synthetic histone H3K9 succinyllysine peptide

substrate: a synthetic GLUD1 peptide malonylated at 'Lys-503'

substrate: a synthetic GLUD1 peptide succinylated at 'Lys-503'

substrate: a synthetic ACSS1 peptide malonylated at 'Lys-628'

substrate: a synthetic ACSS1 peptide succinylated at 'Lys-628'

source: Reference

value: Interacts with CPS1 (By similarity). Interacts with PCCA (PubMed:23438705). Monomer (PubMed:17355872). Homodimer (PubMed:17355872). Forms homodimers upon suramin binding (PubMed:17355872)

value: Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus

value: Mitochondrion matrix

value: Mitochondrion intermembrane space

value: Cytoplasm, cytosol

value: Nucleus

molecule: Isoform 1

value: In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity (PubMed:22076378)

value: The mechanism of demalonylation and desuccinylation involves the presence of a 1',2'-cyclic intermediate, suggesting that sirtuins use the ADP-ribose-peptidylamidate mechanism to remove acyl groups from substrate lysine residues

value: Belongs to the sirtuin family. Class III subfamily

description: Mitochondrion

description: Deacetylase sirtuin-type

description: Proton acceptor

description: in isoform 4

description: in isoform 3

description: in isoform 2

description: in isoform 2

description: in dbSNP:rs9464003

description: in dbSNP:rs34162626

description: Abolishes enzyme activity.

description: Increases the KM for desuccinylation.

description: Increases the KM for desuccinylation. Does not affect deacetylase activity.

description: Abolishes desuccinylation and deglutarylation activity.

description: in Ref. 2; BAG63757

title: Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
TISSUE SPECIFICITY

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4)

authors:
Bechtel S.
Rosenfelder H.
Duda A.
Schmidt C.P.
Ernst U.
Wellenreuther R.
Mehrle A.
Schuster C.
Bahr A.
Bloecker H.
Heubner D.
Hoerlein A.
Michel G.
Wedler H.
Koehrer K.
Ottenwaelder B.
Poustka A.
Wiemann S.
Schupp I.

title: The full-ORF clone resource of the German cDNA consortium.

authors:
Mungall A.J.
Palmer S.A.
Sims S.K.
Edwards C.A.
Ashurst J.L.
Wilming L.
Jones M.C.
Horton R.
Hunt S.E.
Scott C.E.
Gilbert J.G.R.
Clamp M.E.
Bethel G.
Milne S.
Ainscough R.
Almeida J.P.
Ambrose K.D.
Andrews T.D.
Ashwell R.I.S.
Babbage A.K.
Bagguley C.L.
Bailey J.
Banerjee R.
Barker D.J.
Barlow K.F.
Bates K.
Beare D.M.
Beasley H.
Beasley O.
Bird C.P.
Blakey S.E.
Bray-Allen S.
Brook J.
Brown A.J.
Brown J.Y.
Burford D.C.
Burrill W.
Burton J.
Carder C.
Carter N.P.
Chapman J.C.
Clark S.Y.
Clark G.
Clee C.M.
Clegg S.
Cobley V.
Collier R.E.
Collins J.E.
Colman L.K.
Corby N.R.
Coville G.J.
Culley K.M.
Dhami P.
Davies J.
Dunn M.
Earthrowl M.E.
Ellington A.E.
Evans K.A.
Faulkner L.
Francis M.D.
Frankish A.
Frankland J.
French L.
Garner P.
Garnett J.
Ghori M.J.
Gilby L.M.
Gillson C.J.
Glithero R.J.
Grafham D.V.
Grant M.
Gribble S.
Griffiths C.
Griffiths M.N.D.
Hall R.
Halls K.S.
Hammond S.
Harley J.L.
Hart E.A.
Heath P.D.
Heathcott R.
Holmes S.J.
Howden P.J.
Howe K.L.
Howell G.R.
Huckle E.
Humphray S.J.
Humphries M.D.
Hunt A.R.
Johnson C.M.
Joy A.A.
Kay M.
Keenan S.J.
Kimberley A.M.
King A.
Laird G.K.
Langford C.
Lawlor S.
Leongamornlert D.A.
Leversha M.
Lloyd C.R.
Lloyd D.M.
Loveland J.E.
Lovell J.
Martin S.
Mashreghi-Mohammadi M.
Maslen G.L.
Matthews L.
McCann O.T.
McLaren S.J.
McLay K.
McMurray A.
Moore M.J.F.
Mullikin J.C.
Niblett D.
Nickerson T.
Novik K.L.
Oliver K.
Overton-Larty E.K.
Parker A.
Patel R.
Pearce A.V.
Peck A.I.
Phillimore B.J.C.T.
Phillips S.
Plumb R.W.
Porter K.M.
Ramsey Y.
Ranby S.A.
Rice C.M.
Ross M.T.
Searle S.M.
Sehra H.K.
Sheridan E.
Skuce C.D.
Smith S.
Smith M.
Spraggon L.
Squares S.L.
Steward C.A.
Sycamore N.
Tamlyn-Hall G.
Tester J.
Theaker A.J.
Thomas D.W.
Thorpe A.
Tracey A.
Tromans A.
Tubby B.
Wall M.
Wallis J.M.
West A.P.
White S.S.
Whitehead S.L.
Whittaker H.
Wild A.
Willey D.J.
Wilmer T.E.
Wood J.M.
Wray P.W.
Wyatt J.C.
Young L.
Younger R.M.
Bentley D.R.
Coulson A.
Durbin R.M.
Hubbard T.
Sulston J.E.
Dunham I.
Rogers J.
Beck S.

title: The DNA sequence and analysis of human chromosome 6.

authors:
Mural R.J.
Istrail S.
Sutton G.G.
Florea L.
Halpern A.L.
Mobarry C.M.
Lippert R.
Walenz B.
Shatkay H.
Dew I.
Miller J.R.
Flanigan M.J.
Edwards N.J.
Bolanos R.
Fasulo D.
Halldorsson B.V.
Hannenhalli S.
Turner R.
Yooseph S.
Lu F.
Nusskern D.R.
Shue B.C.
Zheng X.H.
Zhong F.
Delcher A.L.
Huson D.H.
Kravitz S.A.
Mouchard L.
Reinert K.
Remington K.A.
Clark A.G.
Waterman M.S.
Eichler E.E.
Adams M.D.
Hunkapiller M.W.
Myers E.W.
Venter J.C.

title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

authors:
Michishita E.
Park J.Y.
Burneskis J.M.
Barrett J.C.
Horikawa I.

title: Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins.

authors:
Schlicker C.
Gertz M.
Papatheodorou P.
Kachholz B.
Becker C.F.W.
Steegborn C.

title: Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5.

authors:
Burkard T.R.
Planyavsky M.
Kaupe I.
Breitwieser F.P.
Buerckstuemmer T.
Bennett K.L.
Superti-Furga G.
Colinge J.

title: Initial characterization of the human central proteome.

referencePositions: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]

authors:
Matsushita N.
Yonashiro R.
Ogata Y.
Sugiura A.
Nagashima S.
Fukuda T.
Inatome R.
Yanagi S.

title: Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms.

referencePositions:
ALTERNATIVE SPLICING (ISOFORMS 1 AND 2)
SUBCELLULAR LOCATION (ISOFORMS 1 AND 2)

authors:
Peng C.
Lu Z.
Xie Z.
Cheng Z.
Chen Y.
Tan M.
Luo H.
Zhang Y.
He W.
Yang K.
Zwaans B.M.
Tishkoff D.
Ho L.
Lombard D.
He T.C.
Dai J.
Verdin E.
Ye Y.
Zhao Y.

title: The first identification of lysine malonylation substrates and its regulatory enzyme.

referencePositions:
FUNCTION
NAD-BINDING
MUTAGENESIS OF HIS-158

authors:
Fischer F.
Gertz M.
Suenkel B.
Lakshminarasimhan M.
Schutkowski M.
Steegborn C.

title: Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition.

referencePositions:
ACTIVITY REGULATION
MUTAGENESIS OF THR-69 AND ARG-105

authors:
Lin Z.F.
Xu H.B.
Wang J.Y.
Lin Q.
Ruan Z.
Liu F.B.
Jin W.
Huang H.H.
Chen X.

title: SIRT5 desuccinylates and activates SOD1 to eliminate ROS.

authors:
Wirth M.
Karaca S.
Wenzel D.
Ho L.
Tishkoff D.
Lombard D.B.
Verdin E.
Urlaub H.
Jedrusik-Bode M.
Fischle W.

title: Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals interact with pyruvate carboxylase and other acetylated biotin-dependent carboxylases.

authors:
Park J.
Chen Y.
Tishkoff D.X.
Peng C.
Tan M.
Dai L.
Xie Z.
Zhang Y.
Zwaans B.M.
Skinner M.E.
Lombard D.B.
Zhao Y.

title: SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways.

authors:
Tan M.
Peng C.
Anderson K.A.
Chhoy P.
Xie Z.
Dai L.
Park J.
Chen Y.
Huang H.
Zhang Y.
Ro J.
Wagner G.R.
Green M.F.
Madsen A.S.
Schmiesing J.
Peterson B.S.
Xu G.
Ilkayeva O.R.
Muehlbauer M.J.
Braulke T.
Muehlhausen C.
Backos D.S.
Olsen C.A.
McGuire P.J.
Pletcher S.D.
Lombard D.B.
Hirschey M.D.
Zhao Y.

title: Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.

referencePositions:
FUNCTION
CATALYTIC ACTIVITY
MUTAGENESIS OF HIS-158

authors:
Bian Y.
Song C.
Cheng K.
Dong M.
Wang F.
Huang J.
Sun D.
Wang L.
Ye M.
Zou H.

title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

authors:
Yang X.
Wang Z.
Li X.
Liu B.
Liu M.
Liu L.
Chen S.
Ren M.
Wang Y.
Yu M.
Wang B.
Zou J.
Zhu W.G.
Yin Y.
Gu W.
Luo J.

title: SHMT2 desuccinylation by SIRT5 drives cancer cell proliferation.

title: Crystal structure of human sirtuin homolog 5 in complex with NAD.

referencePositions: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD AND ZINC IONS

authors:
Schuetz A.
Min J.
Antoshenko T.
Wang C.-L.
Allali-Hassani A.
Dong A.
Loppnau P.
Vedadi M.
Bochkarev A.
Sternglanz R.
Plotnikov A.N.

title: Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin.

referencePositions: X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 34-302 IN COMPLEXES WITH ZINC IONS; SURAMIN AND ADP-RIBOSE

authors:
Du J.
Zhou Y.
Su X.
Yu J.J.
Khan S.
Jiang H.
Kim J.
Woo J.
Kim J.H.
Choi B.H.
He B.
Chen W.
Zhang S.
Cerione R.A.
Auwerx J.
Hao Q.
Lin H.

title: Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase.

referencePositions: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-302 IN COMPLEX WITH NAD; ZINC IONS AND SUCCINYLATED PEPTIDE

referencePositions: MUTAGENESIS OF TYR-102; ARG-105 AND HIS-158

authors:
Zhou Y.
Zhang H.
He B.
Du J.
Lin H.
Cerione R.A.
Hao Q.

title: The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5).

authors:
Szczepankiewicz B.G.
Dai H.
Koppetsch K.J.
Qian D.
Jiang F.
Mao C.
Perni R.B.

title: Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5.

referencePositions: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 36-302 IN COMPLEX WITH CARBA-NAD AND ZINC IONS

authors:
Gertz M.
Nguyen G.T.
Fischer F.
Suenkel B.
Schlicker C.
Franzel B.
Tomaschewski J.
Aladini F.
Becker C.
Wolters D.
Steegborn C.

title: A molecular mechanism for direct sirtuin activation by resveratrol.

referencePositions: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 34-302 IN COMPLEX WITH PROTEIN PEPTIDE; ZINC IONS AND RESVERATROL

value: 8 GO annotations based on evolutionary models

value: Transcriptional activation of mitochondrial biogenesis

value: Expressed in diaphragm and 203 other cell types or tissues

value: F:histone deacetylase activity, NAD-dependent

value: F:NAD-dependent protein lysine deacetylase activity

value: P:negative regulation of cardiac muscle cell apoptotic process

value: P:negative regulation of reactive oxygen species metabolic process

value: P:regulation of ketone biosynthetic process

value: NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED


value: Vesicle-associated membrane protein-associated protein A

value: VAMP-A

value: VAMP-associated protein A

value: VAP-A

value: 33 kDa VAMP-associated protein

value: VAPA

value: Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMed:32344433, PubMed:33124732). STARD3-VAPA interaction enables cholesterol transfer from the ER to endosomes (PubMed:33124732). Via interaction with WDR44 participates in neosynthesized protein export (PubMed:32344433). In addition, recruited to the plasma membrane through OSBPL3 binding (PubMed:25447204). The OSBPL3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:25447204). With OSBPL3, may regulate ER morphology (PubMed:16143324). May play a role in vesicle trafficking (PubMed:11511104, PubMed:19289470)

value: Homodimer; disulfide-linked (PubMed:11511104, PubMed:33124732). Heterodimer with VAPB (PubMed:11511104). Interacts with VAMP1, VAMP2, STX1A, BET1, SEC22C and with the C-terminal domain of OCLN (PubMed:10523508, PubMed:11511104, PubMed:9657962). Interacts (via MSP domain) with OSBPL1A (via FFAT motif) (PubMed:33124732). Interacts (via MSP domain) with ZFYVE27; may retain ZFYVE27 in the endoplasmic reticulum and regulate its function in cell projections formation (PubMed:19289470, PubMed:21976701). Interacts with OSBP (PubMed:20178991). Interacts (via C-terminus) with RSAD2/viperin (via C-terminus) (PubMed:21957124). Interacts with IFITM3 (PubMed:23601107). Interacts with OSBPL3 (phosphorylated form) (PubMed:16143324, PubMed:25447204). Interacts with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701). Interacts (via MSP domain) with STARD3 (via phosphorylated FFAT motif); this interaction recruits VAPA to the endosome (PubMed:24105263, PubMed:33124732). Interacts with STARD3NL (via FFAT motif) (PubMed:24105263). Interacts with CERT1 (PubMed:16895911). Interacts with PLEKHA3 and SACM1L to form a ternary complex (PubMed:30659099). Interacts with VPS13A (via FFAT motif) (PubMed:30741634). Interacts with RB1CC1 (via phosphorylated FFAT motif), MIGA2 (via phosphorylated FFAT motif), RMDN3 (via phosphorylated FFAT motif), KCNB1 (via phosphorylated FFAT motif) and KCNB2 (via phosphorylated FFAT motif) (PubMed:33124732). Interacts (via MSP domain) with WDR44 (via FFAT-like motif); the interactions connect the endoplasmic reticulum (ER) with the endosomal tubule (PubMed:32344433)

value: (Microbial infection) Interacts with HCV protein NS5A and NS5B (PubMed:21957124)

geneName: APOD

geneName: CFTR

geneName: EBP

geneName: EGFR

geneName: OSBP

geneName: VAPB

commentType: SUBCELLULAR LOCATION

value: Present in the plasma membrane and in intracellular vesicles, together with SNARE proteins. May also associate with the cytoskeleton. Colocalizes with OCLN at the tight junction in polarized epithelial cells

value: Endoplasmic reticulum membrane

value: Single-pass type IV membrane protein

value: Cell membrane

value: Cell junction, tight junction

value: Nucleus membrane

value: Ubiquitous

value: The MSP domain binds the FFAT motif of many proteins

value: Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family

commentType: SIMILARITY

sequenceCautionType: Frameshift

type: Initiator methionine

description: Removed

description: Vesicle-associated membrane protein-associated protein A

description: Cytoplasmic

description: Helical; Anchor for type IV membrane protein

description: MSP

description: phosphorylated FFAT motif binding

description: Disordered

description: Basic and acidic residues

description: Involved in binding the phosphorylated serine of the phospho-FFAT motif

description: N-acetylalanine

description: Phosphoserine

description: Phosphothreonine

description: Phosphoserine

description: Phosphoserine

description: Phosphoserine

description: Interchain

description: in isoform 2

description: in dbSNP:rs1044163

description: in dbSNP:rs1127666

description: Impaired interaction with WDR44.

description: Impairs the interaction of the MSP domain with the phosphorylated FFAT motif of STARD3. Does not affect its ability to interact with the conventional FFAT motif of OSBPL1A.

description: Alters interaction with ZFYVE27, impairs interaction with WDR44 and prevents binding to the FFAT motif in target proteins; when associated with D-96.

description: Alters interaction with ZFYVE27, impairs interaction with WDR44 and prevents binding to the FFAT motif in target proteins; when associated with D-94.

description: in Ref. 6; AAC26508 and 8; AAV38424

description: in Ref. 2; AAF72105

authors:
Lapierre L.A.
Tuma P.L.
Navarre J.
Goldenring J.R.
Anderson J.M.

title: VAP-33 localizes to both an intracellular vesicle population and with occludin at the tight junction.

referencePositions:
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
SUBCELLULAR LOCATION
INTERACTION WITH OCLN

authors:
Zhou H.J.
Huang X.W.
Zhou Y.
Hu S.L.
Yuan J.G.
Qiang B.Q.

title: Cloning and isolating human 33kDa Vamp-associated protein cDNA.

authors:
Nusbaum C.
Zody M.C.
Borowsky M.L.
Kamal M.
Kodira C.D.
Taylor T.D.
Whittaker C.A.
Chang J.L.
Cuomo C.A.
Dewar K.
FitzGerald M.G.
Yang X.
Abouelleil A.
Allen N.R.
Anderson S.
Bloom T.
Bugalter B.
Butler J.
Cook A.
DeCaprio D.
Engels R.
Garber M.
Gnirke A.
Hafez N.
Hall J.L.
Norman C.H.
Itoh T.
Jaffe D.B.
Kuroki Y.
Lehoczky J.
Lui A.
Macdonald P.
Mauceli E.
Mikkelsen T.S.
Naylor J.W.
Nicol R.
Nguyen C.
Noguchi H.
O'Leary S.B.
Piqani B.
Smith C.L.
Talamas J.A.
Topham K.
Totoki Y.
Toyoda A.
Wain H.M.
Young S.K.
Zeng Q.
Zimmer A.R.
Fujiyama A.
Hattori M.
Birren B.W.
Sakaki Y.
Lander E.S.

title: DNA sequence and analysis of human chromosome 18.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]

authors:
Mural R.J.
Istrail S.
Sutton G.G.
Florea L.
Halpern A.L.
Mobarry C.M.
Lippert R.
Walenz B.
Shatkay H.
Dew I.
Miller J.R.
Flanigan M.J.
Edwards N.J.
Bolanos R.
Fasulo D.
Halldorsson B.V.
Hannenhalli S.
Turner R.
Yooseph S.
Lu F.
Nusskern D.R.
Shue B.C.
Zheng X.H.
Zhong F.
Delcher A.L.
Huson D.H.
Kravitz S.A.
Mouchard L.
Reinert K.
Remington K.A.
Clark A.G.
Waterman M.S.
Eichler E.E.
Adams M.D.
Hunkapiller M.W.
Myers E.W.
Venter J.C.

title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-199 (ISOFORM 2)

title: Identification of a human homologue of the vesicle-associated membrane protein (VAMP)-associated protein of 33 kDa (VAP-33): a broadly expressed protein that binds to VAMP.

referencePositions: NUCLEOTIDE SEQUENCE [MRNA] OF 8-249 (ISOFORM 1)

authors:
Nishimura Y.
Hayashi M.
Inada H.
Tanaka T.

title: Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins.

authors:
Kalnine N.
Chen X.
Rolfs A.
Halleck A.
Hines L.
Eisenstein S.
Koundinya M.
Raphael J.
Moreira D.
Kelley T.
LaBaer J.
Lin Y.
Phelan M.
Farmer A.

title: Cloning of human full-length CDSs in BD Creator(TM) system donor vector.

referencePositions: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-249 (ISOFORM 1)

title: VAP-A binds promiscuously to both v- and tSNAREs.

referencePositions: INTERACTION WITH VAPB; VAMP1; VAMP2; STX1A; BET1 AND SEC22C

authors:
Lehto M.
Hynynen R.
Karjalainen K.
Kuismanen E.
Hyvaerinen K.
Olkkonen V.M.

title: Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants.

referencePositions:
FUNCTION
INTERACTION WITH OSBPL3
SUBCELLULAR LOCATION

authors:
Kawano M.
Kumagai K.
Nishijima M.
Hanada K.

title: Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT.

authors:
Saita S.
Shirane M.
Natume T.
Iemura S.
Nakayama K.I.

title: Promotion of neurite extension by protrudin requires its interaction with vesicle-associated membrane protein-associated protein.

referencePositions:
FUNCTION
INTERACTION WITH ZFYVE27
MUTAGENESIS OF LYS-94 AND MET-96
SUBCELLULAR LOCATION

authors:
Choudhary C.
Kumar C.
Gnad F.
Nielsen M.L.
Rehman M.
Walther T.C.
Olsen J.V.
Mann M.

title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

referencePositions: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-125

authors:
Matsuzaki F.
Shirane M.
Matsumoto M.
Nakayama K.I.

title: Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation.

authors:
Wang S.
Wu X.
Pan T.
Song W.
Wang Y.
Zhang F.
Yuan Z.

title: Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33.

referencePositions: INTERACTION WITH HCV PROTEIN NS5A AND NS5B (MICROBIAL INFECTION)

authors:
Amini-Bavil-Olyaee S.
Choi Y.J.
Lee J.H.
Shi M.
Huang I.C.
Farzan M.
Jung J.U.

title: The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry.

authors:
Alpy F.
Rousseau A.
Schwab Y.
Legueux F.
Stoll I.
Wendling C.
Spiegelhalter C.
Kessler P.
Mathelin C.
Rio M.C.
Levine T.P.
Tomasetto C.

title: STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the ER.

authors:
Zhou H.
Di Palma S.
Preisinger C.
Peng M.
Polat A.N.
Heck A.J.
Mohammed S.

title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

referencePositions: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166; THR-170; SER-214; SER-216 AND SER-219

referencePositions: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214

authors:
Weber-Boyvat M.
Kentala H.
Lilja J.
Vihervaara T.
Hanninen R.
Zhou Y.
Peranen J.
Nyman T.A.
Ivaska J.
Olkkonen V.M.

title: OSBP-related protein 3 (ORP3) coupling with VAMP-associated protein A regulates R-Ras activity.

authors:
Vaca Jacome A.S.
Rabilloud T.
Schaeffer-Reiss C.
Rompais M.
Ayoub D.
Lane L.
Bairoch A.
Van Dorsselaer A.
Carapito C.

title: N-terminome analysis of the human mitochondrial proteome.

referencePositions: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2

referencePositions: CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]

authors:
Di Mattia T.
Wilhelm L.P.
Ikhlef S.
Wendling C.
Spehner D.
Nomine Y.
Giordano F.
Mathelin C.
Drin G.
Tomasetto C.
Alpy F.

title: Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites.

referencePositions:
IDENTIFICATION BY MASS SPECTROMETRY
MUTAGENESIS OF LYS-94 AND MET-96

authors:
Yeshaw W.M.
van der Zwaag M.
Pinto F.
Lahaye L.L.
Faber A.I.
Gomez-Sanchez R.
Dolga A.M.
Poland C.
Monaco A.P.
van Ijzendoorn S.C.
Grzeschik N.A.
Velayos-Baeza A.
Sibon O.C.

title: Human VPS13A is associated with multiple organelles and influences mitochondrial morphology and lipid droplet motility.

referencePositions:
SUBCELLULAR LOCATION
INTERACTION WITH VPS13A

authors:
Venditti R.
Masone M.C.
Rega L.R.
Di Tullio G.
Santoro M.
Polishchuk E.
Serrano I.C.
Olkkonen V.M.
Harada A.
Medina D.L.
La Montagna R.
De Matteis M.A.

title: The activity of Sac1 across ER-TGN contact sites requires the four-phosphate-adaptor-protein-1.

authors:
Lucken-Ardjomande Haesler S.
Vallis Y.
Pasche M.
McMahon H.T.

title: GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export of E-cadherin, MMP14, and CFTR DeltaF508.

referencePositions: MUTAGENESIS OF 1-MET--VAL-51; LYS-94 AND MET-96

authors:
Furuita K.
Jee J.
Fukada H.
Mishima M.
Kojima C.

title: Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies.

referencePositions:
STRUCTURE BY NMR OF 11-135
INTERACTION WITH OSBP

authors:
Di Mattia T.
Martinet A.
Ikhlef S.
McEwen A.G.
Nomine Y.
Wendling C.
Poussin-Courmontagne P.
Voilquin L.
Eberling P.
Ruffenach F.
Cavarelli J.
Slee J.
Levine T.P.
Drin G.
Tomasetto C.
Alpy F.

title: FFAT motif phosphorylation controls formation and lipid transfer function of inter-organelle contacts.

referencePositions: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 9-134 IN COMPLEX WITH THE PHOSPHO-FFAT MOTIF OF STARD3

referencePositions: INTERACTION WITH STARD3; RB1CC1; MIGA2; RMDN3; KCNB1; KCNB2 AND OSBPL1A

value: 4 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (3 sites)

value: 4 GO annotations based on evolutionary models

value: Insertion of tail-anchored proteins into the endoplasmic reticulum membrane

value: Presynaptic clusters and postsynaptic densities

value: Expressed in endothelial cell and 213 other cell types or tissues

value: P:endoplasmic reticulum to Golgi vesicle-mediated transport

value: P:endoplasmic reticulum-plasma membrane tethering

value: P:host-mediated activation of viral genome replication

value: P:host-mediated suppression of viral genome replication

value: P:positive regulation of canonical NF-kappaB signal transduction

value: P:protein localization to endoplasmic reticulum

value: vesicle-associated membrane protein-associated protein A isoform X1

value: VESICLE-ASSOCIATED MEMBRANE PROTEIN-ASSOCIATED PROTEIN

value: VESICLE-ASSOCIATED MEMBRANE PROTEIN-ASSOCIATED PROTEIN A