iUUCD 2.0 - integrated annotations for ubiquitin and ubiquitin-like conjugation database

Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEO	ArrayExpress
DNA & RNA Element
microRNA	TRANSFAC	RAID2
Protein-protein Interaction
IID	iRefIndex	PINA	HINT
Mentha
Drug and target
GRAC
Post-translational Modifications (PTMs)
CPLM	dbPAF	PhosphositePlus	dbPTM
UniProt
Protein Expression/Proteomics
GPMDB

Status

Unreviewed

Classification

Family	E-Value	Score	Start	End
UBD/SH3	1.40e-15	57.3	66	122

Active Site

Position(s)	Description	Evidence
N/A	N/A	N/A

Domain Profile

UBD/SH3

   S: 4    ekvqvlydyeaqnddeLtlkkGdvvlviekeeqdegWlkgvkelegkrGlfPenFvekle 63
           + v +ly+y++ + d+L++kkG++++v+   e+ ++W+k+++  ++++G++P+n+v+k++
   Q: 66   DIVVALYPYDGIHPDDLSFKKGEKMKVL---EEHGEWWKAKSLSSKREGFIPSNYVAKVN 122
           5799************************...999************************97 PP

Organism

Rattus norvegicus

Functional Description
(View)

Functional Description

Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B (By similarity). Phosphorylates LPXN on 'Tyr-72' (By similarity). Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation.

Protein Sequence
(Fasta)

MGCIKSKRKD NLNDDGVDMK TQPVRNTDRT IYVRDPTSNK QQRPVPESQL LPGQRFQAKD 60
PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW KAKSLSSKRE GFIPSNYVAK 120

It may take some time, please wait.

Nucleotide Sequence
(Fasta)

AGCCGGGCCT GGGAGCCTCC CGGCCAACGT TCTGCAGCTG GTAGCCTGCT GCAGGCTGGG 60
CACTGTCCCC CGAGCAGTGT GCCCTTAAGT ACTGGCTAAG CGTCCTACCA CCCGGGCCCG 120

It may take some time, please wait.

Sequence Source

Ensembl

Keyword

KW-1064--Adaptive immunity
KW-0025--Alternative splicing
KW-0067--ATP-binding
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0333--Golgi apparatus
KW-0391--Immunity
KW-0395--Inflammatory response
KW-0399--Innate immunity
KW-0418--Kinase
KW-0449--Lipoprotein
KW-0472--Membrane
KW-0519--Myristate
KW-0547--Nucleotide-binding
KW-0539--Nucleus
KW-0564--Palmitate
KW-0597--Phosphoprotein
KW-0656--Proto-oncogene
KW-1185--Reference proteome
KW-0727--SH2 domain
KW-0728--SH3 domain
KW-0808--Transferase
KW-0829--Tyrosine-protein kinase
KW-0832--Ubl conjugation

Interpro

IPR011009--Kinase-like_dom
IPR000719--Prot_kinase_dom
IPR017441--Protein_kinase_ATP_BS
IPR001245--Ser-Thr/Tyr_kinase_cat_dom
IPR000980--SH2
IPR001452--SH3_domain
IPR008266--Tyr_kinase_AS
IPR020635--Tyr_kinase_cat_dom

PROSITE

PS00107--PROTEIN_KINASE_ATP
PS50011--PROTEIN_KINASE_DOM
PS00109--PROTEIN_KINASE_TYR
PS50001--SH2
PS50002--SH3

Pfam

PF07714--Pkinase_Tyr
PF00017--SH2
PF00018--SH3_1

PRINTS

PR00401--SH2DOMAIN
PR00452--SH3DOMAIN
PR00109--TYRKINASE

SMART

SM00252--SH2
SM00326--SH3
SM00219--TyrKc

Gene Ontology

GO:0005913--C:cell-cell adherens junction
GO:0005737--C:cytoplasm
GO:0070062--C:extracellular exosome
GO:0031234--C:extrinsic component of cytoplasmic side of plasma membrane
GO:0005794--C:Golgi apparatus
GO:0034666--C:integrin alpha2-beta1 complex
GO:0042629--C:mast cell granule
GO:0016020--C:membrane
GO:0045121--C:membrane raft
GO:0030061--C:mitochondrial crista
GO:0005758--C:mitochondrial intermembrane space
GO:0031966--C:mitochondrial membrane
GO:0005634--C:nucleus
GO:0048471--C:perinuclear region of cytoplasm
GO:0005886--C:plasma membrane
GO:0014069--C:postsynaptic density
GO:0005524--F:ATP binding
GO:0019899--F:enzyme binding
GO:0043015--F:gamma-tubulin binding
GO:0043208--F:glycosphingolipid binding
GO:0005178--F:integrin binding
GO:0016301--F:kinase activity
GO:0004715--F:non-membrane spanning protein tyrosine kinase activity
GO:0051219--F:phosphoprotein binding
GO:0005161--F:platelet-derived growth factor receptor binding
GO:0032403--F:protein complex binding
GO:0004713--F:protein tyrosine kinase activity
GO:0005102--F:receptor binding
GO:0031625--F:ubiquitin protein ligase binding
GO:0002250--P:adaptive immune response
GO:0001782--P:B cell homeostasis
GO:0050853--P:B cell receptor signaling pathway
GO:0016477--P:cell migration
GO:0006974--P:cellular response to DNA damage stimulus
GO:0031668--P:cellular response to extracellular stimulus
GO:0034605--P:cellular response to heat
GO:0071300--P:cellular response to retinoic acid
GO:0006935--P:chemotaxis
GO:0050663--P:cytokine secretion
GO:0097028--P:dendritic cell differentiation
GO:0030218--P:erythrocyte differentiation
GO:0002774--P:Fc receptor mediated inhibitory signaling pathway
GO:0002431--P:Fc receptor mediated stimulatory signaling pathway
GO:0002553--P:histamine secretion by mast cell
GO:0002768--P:immune response-regulating cell surface receptor signaling pathway
GO:0045087--P:innate immune response
GO:0035556--P:intracellular signal transduction
GO:0031663--P:lipopolysaccharide-mediated signaling pathway
GO:0030889--P:negative regulation of B cell proliferation
GO:0008285--P:negative regulation of cell proliferation
GO:0070373--P:negative regulation of ERK1 and ERK2 cascade
GO:1902532--P:negative regulation of intracellular signal transduction
GO:0043407--P:negative regulation of MAP kinase activity
GO:0070667--P:negative regulation of mast cell proliferation
GO:0002762--P:negative regulation of myeloid leukocyte differentiation
GO:0001933--P:negative regulation of protein phosphorylation
GO:0034136--P:negative regulation of toll-like receptor 2 signaling pathway
GO:0034144--P:negative regulation of toll-like receptor 4 signaling pathway
GO:0031175--P:neuron projection development
GO:0014003--P:oligodendrocyte development
GO:0038083--P:peptidyl-tyrosine autophosphorylation
GO:0002576--P:platelet degranulation
GO:0050861--P:positive regulation of B cell receptor signaling pathway
GO:0030335--P:positive regulation of cell migration
GO:0008284--P:positive regulation of cell proliferation
GO:2000670--P:positive regulation of dendritic cell apoptotic process
GO:0060369--P:positive regulation of Fc receptor mediated stimulatory signaling pathway
GO:0060252--P:positive regulation of glial cell proliferation
GO:0070668--P:positive regulation of mast cell proliferation
GO:0010976--P:positive regulation of neuron projection development
GO:0070447--P:positive regulation of oligodendrocyte progenitor proliferation
GO:0043552--P:positive regulation of phosphatidylinositol 3-kinase activity
GO:0042327--P:positive regulation of phosphorylation
GO:0070304--P:positive regulation of stress-activated protein kinase signaling cascade
GO:0042531--P:positive regulation of tyrosine phosphorylation of STAT protein
GO:0002902--P:regulation of B cell apoptotic process
GO:0050855--P:regulation of B cell receptor signaling pathway
GO:0033628--P:regulation of cell adhesion mediated by integrin
GO:0001817--P:regulation of cytokine production
GO:0050707--P:regulation of cytokine secretion
GO:0070372--P:regulation of ERK1 and ERK2 cascade
GO:0045646--P:regulation of erythrocyte differentiation
GO:0050727--P:regulation of inflammatory response
GO:0033003--P:regulation of mast cell activation
GO:0043304--P:regulation of mast cell degranulation
GO:0090025--P:regulation of monocyte chemotaxis
GO:0090330--P:regulation of platelet aggregation
GO:0051279--P:regulation of release of sequestered calcium ion into cytosol
GO:0043200--P:response to amino acid
GO:0048678--P:response to axon injury
GO:0009743--P:response to carbohydrate
GO:0042493--P:response to drug
GO:0009725--P:response to hormone
GO:0032868--P:response to insulin
GO:0014070--P:response to organic cyclic compound
GO:0043434--P:response to peptide hormone
GO:0006991--P:response to sterol depletion
GO:0009636--P:response to toxic substance
GO:0002513--P:tolerance induction to self antigen
GO:0007169--P:transmembrane receptor protein tyrosine kinase signaling pathway

KEGG

rno:81515

Orthology

iUUCD ID	Species	Identity	E-value	Score
IUUC-Aml-001812	Ailuropoda melanoleuca	97.27	0.00e+00	1047.00
IUUC-Apl-004139	Anas platyrhynchos	88.78	0.00e+00	951.00
IUUC-Aca-004333	Anolis carolinensis	86.58	0.00e+00	929.00
IUUC-Ame-011257	Astyanax mexicanus	76.31	0.00e+00	822.00
IUUC-Bta-013257	Bos taurus	96.48	0.00e+00	1043.00
IUUC-Cja-018827	Callithrix jacchus	95.90	0.00e+00	1033.00
IUUC-Cfa-020816	Canis familiaris	97.07	0.00e+00	1044.00
IUUC-Cpo-021423	Cavia porcellus	96.68	0.00e+00	1037.00
IUUC-Csa-024244	Chlorocebus sabaeus	96.48	0.00e+00	1039.00
IUUC-Dre-028518	Danio rerio	76.07	0.00e+00	811.00
IUUC-Dno-029322	Dasypus novemcinctus	97.85	0.00e+00	1047.00
IUUC-Dor-030706	Dipodomys ordii	87.11	0.00e+00	915.00
IUUC-Eca-034193	Equus caballus	97.27	0.00e+00	1045.00
IUUC-Fal-037273	Ficedula albicollis	89.28	0.00e+00	962.00
IUUC-Gmo-039677	Gadus morhua	75.11	0.00e+00	723.00
IUUC-Gga-040417	Gallus gallus	85.35	0.00e+00	909.00
IUUC-Gac-042490	Gasterosteus aculeatus	71.71	0.00e+00	791.00
IUUC-Ggo-045096	Gorilla gorilla	96.09	0.00e+00	1036.00
IUUC-Hsa-046214	Homo sapiens	96.09	0.00e+00	1036.00
IUUC-Itr-048354	Ictidomys tridecemlineatus	98.24	0.00e+00	1056.00
IUUC-Lch-049991	Latimeria chalumnae	80.97	0.00e+00	861.00
IUUC-Loc-052309	Lepisosteus oculatus	78.10	0.00e+00	842.00
IUUC-Laf-053568	Loxodonta africana	96.68	0.00e+00	1040.00
IUUC-Mcc-054849	Macaca mulatta	96.48	0.00e+00	1039.00
IUUC-Meu-056170	Macropus eugenii	78.12	0.00e+00	800.00
IUUC-Mmr-061519	Microcebus murinus	96.68	0.00e+00	1045.00
IUUC-Mdo-062090	Monodelphis domestica	81.84	0.00e+00	890.00
IUUC-Mmu-063760	Mus musculus	98.24	0.00e+00	1050.00
IUUC-Mpu-065677	Mustela putorius furo	96.88	0.00e+00	1045.00
IUUC-Mlu-067386	Myotis lucifugus	96.48	0.00e+00	1039.00
IUUC-Nle-069742	Nomascus leucogenys	96.48	0.00e+00	1040.00
IUUC-Ont-071537	Oreochromis niloticus	73.54	0.00e+00	793.00
IUUC-Oan-073193	Ornithorhynchus anatinus	93.97	0.00e+00	1011.00
IUUC-Ocu-074501	Oryctolagus cuniculus	97.85	0.00e+00	1049.00
IUUC-Ola-086726	Oryzias latipes	69.98	0.00e+00	776.00
IUUC-Oga-088069	Otolemur garnettii	96.11	0.00e+00	1038.00
IUUC-Oar-090091	Ovis aries	96.48	0.00e+00	1041.00
IUUC-Ptr-091409	Pan troglodytes	96.09	0.00e+00	1036.00
IUUC-Pan-092268	Papio anubis	96.48	0.00e+00	1039.00
IUUC-Psi-093685	Pelodiscus sinensis	88.39	0.00e+00	950.00
IUUC-Pfo-096217	Poecilia formosa	73.15	0.00e+00	796.00
IUUC-Pab-098601	Pongo abelii	96.29	0.00e+00	1038.00
IUUC-Pva-102160	Pteropus vampyrus	85.77	0.00e+00	897.00
IUUC-Sha-106643	Sarcophilus harrisii	92.80	0.00e+00	1003.00
IUUC-Sar-113555	Sorex araneus	94.44	3.00e-173	600.00
IUUC-Ssc-116317	Sus scrofa	90.45	0.00e+00	963.00
IUUC-Tgu-116865	Taeniopygia guttata	89.47	0.00e+00	964.00
IUUC-Tru-118284	Takifugu rubripes	71.79	0.00e+00	783.00
IUUC-Tsy-119440	Tarsius syrichta	92.19	0.00e+00	977.00
IUUC-Tni-120005	Tetraodon nigroviridis	70.76	0.00e+00	771.00
IUUC-Ttr-128481	Tursiops truncatus	82.81	0.00e+00	852.00
IUUC-Xtr-131907	Xenopus tropicalis	77.18	0.00e+00	808.00

Created Date

25-Jun-2017

Functional Description

Protein Fasta Sequence

Nucleotide Fasta Sequence