AiPD: Autoinhibited Protein Database

P49427

Gene name	CDC34 (UBCH3, UBE2R1)
Protein name	Ubiquitin-conjugating enzyme E2 R1
Names	(E3-independent) E2 ubiquitin-conjugating enzyme R1, E2 ubiquitin-conjugating enzyme R1, Ubiquitin-conjugating enzyme E2-32 kDa complementing, Ubiquitin-conjugating enzyme E2-CDC34, Ubiquitin-protein ligase R1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:997
EC number	2.3.2.23: Aminoacyltransferases
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

142-236 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

142-236 (Predicted disordered autoinhibitory region)

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell Systems, 2, 89-100

Autoinhibited structure

Activated structure

5 structures for P49427

Entry ID	Method	Resolution	Chain	Position	Source
2OB4	X-ray	240 A	A	7-184	PDB
3RZ3	X-ray	230 A	A/B/C/D	7-184	PDB
4MDK	X-ray	261 A	A/B/C/D	7-184	PDB
7M2K	X-ray	247 A	A/C/E/G	7-184	PDB
AF-P49427-F1	Predicted				AlphaFoldDB

168 variants for P49427

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs748895553 CA9016733	3	R>P		No	ClinGen ExAC gnomAD
rs772391519 CA9016734	4	P>S		No	ClinGen ExAC TOPMed gnomAD
rs143937615 CA9016735	6	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs747285861 CA9016736	7	P>R		No	ClinGen ExAC gnomAD
rs1490829755 CA402858991	7	P>S		No	ClinGen gnomAD
rs1160918318 CA402859081	12	A>T		No	ClinGen TOPMed
rs1419118549 CA402859097	12	A>V		No	ClinGen TOPMed
TCGA novel	14	L>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1254177049 CA402859154	17	L>F		No	ClinGen TOPMed
CA402859164 rs1188580719	17	L>P	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA303892264 rs866955717	18	K>R		No	ClinGen gnomAD
TCGA novel	18	K>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs777031141 CA9016738	22	E>K		No	ClinGen ExAC gnomAD
CA402859271 rs1425868708	23	E>K		No	ClinGen TOPMed gnomAD
CA402859272 rs1425868708	23	E>Q		No	ClinGen TOPMed gnomAD
CA9016740 rs765510335	24	P>L		No	ClinGen ExAC TOPMed gnomAD
CA9016739 rs759742031	24	P>S		No	ClinGen ExAC gnomAD
CA402859354 rs1301290037	29	R>L		No	ClinGen TOPMed
CA402859378 rs1373021081	32	L>V		No	ClinGen TOPMed
CA9016744 rs148639611	35	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA9016746 rs757298312	36	G>D		No	ClinGen ExAC gnomAD
rs975917752 CA303892296	36	G>S		No	ClinGen Ensembl
rs767394877 CA9016747	37	D>E		No	ClinGen ExAC gnomAD
CA9016749 rs755819680	38	L>R		No	ClinGen ExAC gnomAD
rs750297342 CA9016748	38	L>V		No	ClinGen ExAC gnomAD
rs778328367 CA9016753	44	A>V		No	ClinGen ExAC gnomAD
rs1403138220 CA402859538	46	F>L		No	ClinGen gnomAD
rs1394129659 CA402859546	47	G>R		No	ClinGen TOPMed
CA402859582 rs1345368372	49	P>L	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
TCGA novel	49	P>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	52	Y>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA9016758 rs746240753	56	G>S		No	ClinGen ExAC gnomAD
CA9016781 rs768815065	61	R>C	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs774565109 CA9016782	61	R>H		No	ClinGen ExAC TOPMed gnomAD
CA9016783 rs761984062	63	K>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
CA9016784 rs146663310	66	I>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1003265423 CA303895298	67	D>Y		No	ClinGen Ensembl
CA402861696 rs1305056777	73	P>S		No	ClinGen gnomAD
rs1035638093 CA303895312	74	A>V		No	ClinGen TOPMed gnomAD
CA9016787 rs375521090	76	R>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen 1000Genomes ESP ExAC NCI-TCGA TOPMed gnomAD
rs1568330110 CA402861727	76	R>W	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen Ensembl NCI-TCGA
TCGA novel	80	K>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	82	W>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1600423052 CA402861813	83	H>P		No	ClinGen Ensembl
CA9016840 rs765674047	92	V>L		No	ClinGen ExAC gnomAD
CA9016839 rs765674047	92	V>M		No	ClinGen ExAC gnomAD
rs757316651 CA9016844	97	L>P		No	ClinGen ExAC gnomAD
CA9016845 rs200517034	98	H>P		No	ClinGen ExAC gnomAD
rs1403833110 CA402862091	99	P>L		No	ClinGen TOPMed
rs1309948530 CA402862101	100	P>L		No	ClinGen gnomAD
CA402862120 rs1332343229	101	V>G		No	ClinGen gnomAD
rs146527192 CA9016849	101	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1326670665 CA402862132	102	D>E		No	ClinGen TOPMed gnomAD
CA402862123 rs768235050	102	D>H		No	ClinGen ExAC TOPMed gnomAD
CA9016850 rs768235050	102	D>Y		No	ClinGen ExAC TOPMed gnomAD
CA402862137 rs1225072936	103	D>N		No	ClinGen gnomAD
rs773893349 CA9016851	104	P>H		No	ClinGen ExAC gnomAD
CA9016854 rs772825347	107	G>A		No	ClinGen ExAC gnomAD
rs1453268355 CA402862220	108	E>K		No	ClinGen gnomAD
rs1220347807 CA402862346	117	T>M		No	ClinGen TOPMed
CA9016857 rs753053260	118	Q>R		No	ClinGen ExAC gnomAD
rs1464970251 CA402862377	119	N>T		No	ClinGen gnomAD
rs1274501561 CA402862388	120	V>I		No	ClinGen TOPMed
rs376731647 CA402862403	121	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
CA402862416 rs1306892010	121	R>T		No	ClinGen gnomAD
rs564209470 CA9016909	123	I>V		No	ClinGen 1000Genomes ExAC gnomAD
TCGA novel	124	L>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA402862942 rs11557525	128	I>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs1218171541 CA402862993	133	E>K		No	ClinGen gnomAD
CA402863074 rs1600425607	137	F>L		No	ClinGen Ensembl
rs745378933 CA9016918	137	F>S		No	ClinGen ExAC gnomAD
rs749435711	137	F>missing	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	NCI-TCGA
CA303896888 rs992229990	139	P>S		No	ClinGen Ensembl
CA402863102 rs1462106053	140	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
rs1568330806 CA402863190	144	A>T		No	ClinGen Ensembl
rs1412183232 CA402863223	146	V>M		No	ClinGen gnomAD
CA402863300 rs1431255257	149	R>K		No	ClinGen gnomAD
rs1414962637 CA402863304	149	R>S		No	ClinGen gnomAD
rs549379010 CA9016925	150	K>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1186468318 CA402863444	157	K>N		No	ClinGen TOPMed
rs1600425711 CA402863449	158	D>H		No	ClinGen Ensembl
CA9016929 rs373877648	159	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA9016928 rs373877648	159	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel	159	R>W	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA9016930 rs368089180	162	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA9016931 rs763970240	165	I>T		No	ClinGen ExAC gnomAD
TCGA novel	166	R>W	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA402865849 rs1272691409	167	K>E		No	ClinGen gnomAD
rs1381254137 CA402865853	167	K>M		No	ClinGen TOPMed
rs956067449 CA402865888	169	V>F		No	ClinGen Ensembl
rs956067449 CA303899744	169	V>I		No	ClinGen Ensembl
CA303899745 rs1050890129	173	K>M		No	ClinGen TOPMed
rs1267183464 CA402866002	175	D>G		No	ClinGen TOPMed gnomAD
rs1267183464 CA402866003	175	D>V		No	ClinGen TOPMed gnomAD
rs757696666 CA9016995	176	A>T		No	ClinGen ExAC TOPMed gnomAD
CA303899752 rs917167001	176	A>V		No	ClinGen Ensembl
rs372269784 CA9016997	177	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs756462163 CA9016998	178	R>H		No	ClinGen ExAC gnomAD
rs756462163 CA402866047	178	R>L		No	ClinGen ExAC gnomAD
rs1293891976 CA402866079	180	G>C		No	ClinGen TOPMed gnomAD
rs1293891976 CA402866081	180	G>S		No	ClinGen TOPMed gnomAD
CA303899785 rs76720850	181	V>L		No	ClinGen ESP ExAC gnomAD
rs76720850 CA9017000	181	V>M		No	ClinGen ESP ExAC gnomAD
rs1600432311 CA402866110	182	K>Q		No	ClinGen Ensembl
rs748241028 CA9017003	184	P>S		No	ClinGen ExAC gnomAD
CA402866189 rs1227684760	186	T>M	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA gnomAD
CA402866193 rs1323726074	187	L>V		No	ClinGen gnomAD
rs1265199250 CA402866210	188	A>T		No	ClinGen gnomAD
CA9017008 rs776469357	189	E>K		No	ClinGen ExAC gnomAD
rs764877152 CA402866293	191	C>*		No	ClinGen ExAC TOPMed gnomAD
CA9017009 rs759186036	191	C>Y		No	ClinGen ExAC TOPMed gnomAD
rs774925566 CA9017011	192	V>M	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA9017013 rs762396271	194	T>N		No	ClinGen ExAC TOPMed gnomAD
CA9017012 rs762396271	194	T>S		No	ClinGen ExAC TOPMed gnomAD
CA402866458 rs1257631281	195	K>Q		No	ClinGen Ensembl
CA402866541 rs1165104526	196	A>S		No	ClinGen TOPMed gnomAD
CA402866534 rs1165104526	196	A>T		No	ClinGen TOPMed gnomAD
rs147105441 CA9017017	196	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA9017019 rs779289790	197	P>L		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	197	P>Q	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1167681324 CA402866589	198	A>S		No	ClinGen TOPMed
rs1167681324 CA402866588	198	A>T		No	ClinGen TOPMed
rs375818778 CA9017021	198	A>V		No	ClinGen ExAC TOPMed gnomAD
CA9017027 rs377177218	200	D>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs556391590 CA9017025	200	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs762703606 CA9017029	201	E>G		No	ClinGen ExAC TOPMed gnomAD
CA9017028 rs201584025	201	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA402866739 rs762703606	201	E>V		No	ClinGen ExAC TOPMed gnomAD
CA402866817 rs1252854872	202	G>V		No	ClinGen TOPMed
CA402866937 CA9017034 rs542019154	206	F>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs369990220 CA9017035	207	Y>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA402867011 rs1161096646	208	D>G		No	ClinGen gnomAD
CA9017038 rs200761288	208	D>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs200761288 CA9017037	208	D>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA402867045 rs1299123897	209	D>E		No	ClinGen TOPMed
rs777711920 CA9017040	209	D>N		No	ClinGen ExAC
rs777711920 CA9017042	209	D>Y		No	ClinGen ExAC
CA402867070 rs1156883031	210	Y>*		No	ClinGen gnomAD
rs751666566 CA9017043	210	Y>C		No	ClinGen ExAC TOPMed gnomAD
rs1360855924 CA402867100	211	Y>*		No	ClinGen TOPMed gnomAD
rs1400107184 CA402867082	211	Y>C		No	ClinGen gnomAD
CA402867133 rs1302352352	212	E>D		No	ClinGen gnomAD
CA9017044 rs757087028	212	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1411986019 CA402867165	213	D>G		No	ClinGen gnomAD
rs1353727792 CA402867140	213	D>N		No	ClinGen TOPMed gnomAD
CA402867203 rs1350306457	214	G>C		No	ClinGen gnomAD
rs1034014803 CA303899936	214	G>D		No	ClinGen TOPMed
CA9017046 rs745626145	215	E>K		No	ClinGen ExAC TOPMed gnomAD
CA9017047 rs563776588	216	V>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1270949054 CA402867312	217	E>G		No	ClinGen TOPMed
CA402867302 rs1254971128	217	E>K		No	ClinGen TOPMed gnomAD
CA9017050 rs748875983	218	E>G		No	ClinGen ExAC gnomAD
CA9017049 rs531877075	218	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA402867319 rs531877075	218	E>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs550012804 CA9017051	219	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs773664509 CA9017052	220	A>V		No	ClinGen ExAC TOPMed gnomAD
CA9017054 rs771514074	221	D>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
CA402867542 rs1338082998	223	C>R		No	ClinGen TOPMed
CA9017058 rs568742634 CA303899976	225	G>R		No	ClinGen 1000Genomes ExAC gnomAD
rs1175449924 CA402867638	226	D>N		No	ClinGen gnomAD
CA303899986 VAR_021277 rs16990650	227	D>H		No	ClinGen UniProt ExAC TOPMed dbSNP gnomAD
CA9017060 rs16990650	227	D>N		No	ClinGen ExAC TOPMed gnomAD
rs201715065 CA9017061	228	E>*		No	ClinGen ExAC TOPMed gnomAD
CA402867701 rs1350136168	228	E>G		No	ClinGen gnomAD
CA9017064 rs751546350	231	S>C		No	ClinGen ExAC gnomAD
CA9017065 rs140384237	232	G>D		No	ClinGen 1000Genomes ExAC gnomAD
rs750335335 CA9017067	233	T>M		No	ClinGen ExAC TOPMed gnomAD
rs376164577 CA9017070	235	E>D		No	ClinGen ESP ExAC gnomAD

No associated diseases with P49427

2 regional properties for P49427

Type	Name	Position	InterPro Accession
conserved_site	Thymidylate kinase, conserved site	95 - 107	IPR018095
domain	Thymidylate kinase-like domain	8 - 200	IPR039430

Functions

		Description
EC Number	2.3.2.23	Aminoacyltransferases
Subcellular Localization	Cytoplasm Nucleus	The phosphorylation of the C-terminal tail plays an important role in mediating nuclear localization Colocalizes with beta-tubulin on mitotic spindles in anaphase
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nuclear speck	A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

3 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
ubiquitin conjugating enzyme activity	Isoenergetic transfer of ubiquitin from one protein to another via the reaction X-ubiquitin + Y -> Y-ubiquitin + X, where both the X-ubiquitin and Y-ubiquitin linkages are thioester bonds between the C-terminal glycine of ubiquitin and a sulfhydryl side group of a cysteine residue.
ubiquitin-protein transferase activity	Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y --> Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages.

13 GO annotations of biological process

Name	Definition
cellular response to interferon-beta	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-beta stimulus. Interferon-beta is a type I interferon.
DNA replication initiation	The process in which DNA-dependent DNA replication is started; this begins with the ATP dependent loading of an initiator complex onto the DNA, this is followed by DNA melting and helicase activity. In bacteria, the gene products that enable the helicase activity are loaded after the initial melting and in archaea and eukaryotes, the gene products that enable the helicase activity are inactive when they are loaded and subsequently activate.
G1/S transition of mitotic cell cycle	The mitotic cell cycle transition by which a cell in G1 commits to S phase. The process begins with the build up of G1 cyclin-dependent kinase (G1 CDK), resulting in the activation of transcription of G1 cyclins. The process ends with the positive feedback of the G1 cyclins on the G1 CDK which commits the cell to S phase, in which DNA replication is initiated.
negative regulation of cAMP-mediated signaling	Any process which stops, prevents, or reduces the frequency, rate or extent of cAMP-mediated signaling.
positive regulation of inclusion body assembly	Any process that increases the rate, frequency, or extent of inclusion body assembly. Inclusion body assembly is the aggregation, arrangement and bonding together of a set of components to form an inclusion body.
positive regulation of neuron apoptotic process	Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process.
proteasome-mediated ubiquitin-dependent protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
protein K48-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 48 of the ubiquitin monomers, is added to a protein. K48-linked ubiquitination targets the substrate protein for degradation.
protein modification process	The covalent alteration of one or more amino acids occurring in proteins, peptides and nascent polypeptides (co-translational, post-translational modifications). Includes the modification of charged tRNAs that are destined to occur in a protein (pre-translation modification).
protein polyubiquitination	Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain.
protein ubiquitination	The process in which one or more ubiquitin groups are added to a protein.
response to growth factor	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a growth factor stimulus.
ubiquitin-dependent protein catabolic process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.

2 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q712K3	UBE2R2	Ubiquitin-conjugating enzyme E2 R2	Homo sapiens (Human)	PR
Q8CFI2	Cdc34	Ubiquitin-conjugating enzyme E2 R1	Mus musculus (Mouse)	PR

10	20	30	40	50	60
MARPLVPSSQ	KALLLELKGL	QEEPVEGFRV	TLVDEGDLYN	WEVAIFGPPN	TYYEGGYFKA
70	80	90	100	110	120
RLKFPIDYPY	SPPAFRFLTK	MWHPNIYETG	DVCISILHPP	VDDPQSGELP	SERWNPTQNV
130	140	150	160	170	180
RTILLSVISL	LNEPNTFSPA	NVDASVMYRK	WKESKGKDRE	YTDIIRKQVL	GTKVDAERDG
190	200	210	220	230
VKVPTTLAEY	CVKTKAPAPD	EGSDLFYDDY	YEDGEVEEEA	DSCFGDDEDD	SGTEES