AiPD: Autoinhibited Protein Database

P52788

Gene name	SMS
Protein name	Spermine synthase
Names	SPMSY, Spermidine aminopropyltransferase
Species	Homo sapiens (Human)
KEGG Pathway	hsa:6611
EC number	2.5.1.22: Transferring alkyl or aryl groups, other than methyl groups
Protein Class

Descriptions

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

Autoinhibitory domains (AIDs)

57-132 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

57-132 (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

3 structures for P52788

Entry ID	Method	Resolution	Chain	Position	Source
3C6K	X-ray	195 A	A/B/C/D	5-366	PDB
3C6M	X-ray	245 A	A/B/C/D	5-366	PDB
AF-P52788-F1	Predicted				AlphaFoldDB

151 variants for P52788

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs1921698887 RCV001169877	5	R>G	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinVar dbSNP
RCV000210586 rs121434610 RCV000012390 CA341122 RCV000414369 VAR_076449	56	G>S	Syndromic X-linked intellectual disability Snyder type Inborn genetic diseases MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs397515549 RCV000055902 VAR_072748 CA345011	58	F>L	Syndromic X-linked intellectual disability Snyder type MRXSSR [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt dbSNP gnomAD
rs397515550 RCV000055903 VAR_076450 RCV003221798 CA345012	67	G>E	Syndromic X-linked intellectual disability Snyder type MRXSSR; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001250132 rs1924243873	110	R>G	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinVar dbSNP
rs1602210346 CA412567201 RCV001007564	130	R>C	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
VAR_076451 rs267607076 CA341124 RCV000012391	132	V>G	Syndromic X-linked intellectual disability Snyder type MRXSSR [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV001171510 rs1924586809	137	D>G	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinVar dbSNP
CA345014 RCV000055905 rs397515551	148	Q>R	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs201275730 RCV000179446 RCV000930025 CA203298 RCV002314661	190	T>I	Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
RCV001310252 rs1924648986	196	I>T	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinVar dbSNP
rs1924650670 RCV001255181	203	G>D	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinVar dbSNP
rs1556001138 CA412568892 RCV000622379	213	P>Q	Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs1556001304 CA412568970 RCV000522772 RCV000509103	222	D>V	SMS-Related Disorder [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
CA10367863 RCV000985012 rs757074790	267	G>R	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
RCV002316156 rs1569354289 CA412570339	274	I>V	Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs755701744 CA10367880 RCV001197950	291	T>K	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV001249470 rs1925241775	302	S>L	Intellectual disability [ClinVar]	Yes	ClinVar dbSNP
RCV000853623 rs1602220706	303	M>missing	Syndromic X-linked intellectual disability Snyder type [ClinVar]	Yes	ClinVar dbSNP
rs397515553 RCV000074415 VAR_076452 CA266199	328	Y>C	Syndromic X-linked intellectual disability Snyder type MRXSSR; mild disease phenotype; a reduced spermine/spermidine ratio is observed in patient lymphoblastoid cells consistent with impaired spermine biosynthesis [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
RCV002368110 rs751460863 CA10367905 RCV001329289	340	E>G	Syndromic X-linked intellectual disability Snyder type Inborn genetic diseases [ClinVar]	Yes	ClinGen ClinVar ExAC dbSNP gnomAD
rs1602172689 RCV000999350	1	M>I		No	ClinVar dbSNP
CA412566991 rs1396816418	7	S>G		No	ClinGen TOPMed
TCGA novel	10	D>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA412567043 rs1224045759	14	G>S		No	ClinGen gnomAD
CA412563523 rs1205649886	19	G>S		No	ClinGen TOPMed
rs760670744 CA327511617	20	E>G		No	ClinGen 1000Genomes
CA327511618 rs150246774	21	T>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA10367718 rs150246774	21	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA10367720 rs775900143	23	L>I		No	ClinGen ExAC TOPMed gnomAD
rs1569347230 CA412563663	27	Q>R		No	ClinGen Ensembl
rs398124179 RCV000081159 CA222784	35	M>K		No	ClinGen ClinVar Ensembl dbSNP
CA10367723 rs776916661	36	A>V		No	ClinGen ExAC gnomAD
rs762162684 CA412563907	37	E>D		No	ClinGen ExAC TOPMed gnomAD
CA10367725 rs377476289	38	S>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA412563986 rs1275353398	41	T>A		No	ClinGen gnomAD
rs1349745882 CA412564019	42	W>*		No	ClinGen gnomAD
CA412564052 rs1226310307	43	Q>H		No	ClinGen TOPMed gnomAD
rs765876946 CA10367728	47	Y>C		No	ClinGen ExAC gnomAD
rs878985300 CA327511619	52	T>A		No	ClinGen Ensembl
CA412564358 rs1408135353	57	S>G		No	ClinGen gnomAD
VAR_071048 CA412565066 rs1394834572	60	N>S		No	ClinGen UniProt dbSNP gnomAD
rs778214794 CA327512028	66	H>R		No	ClinGen Ensembl
CA412565225 rs1381885283	69	V>L		No	ClinGen TOPMed
TCGA novel	69	V>M	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs759109950 CA10367748	71	L>V		No	ClinGen ExAC gnomAD
CA412565339 rs1303527359	75	S>N		No	ClinGen TOPMed
CA10367750 COSM1226907 rs752654736	80	A>V	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA gnomAD
CA412565456 rs1250656927	81	Q>E		No	ClinGen TOPMed gnomAD
rs777583658 CA10367752	81	Q>R		No	ClinGen ExAC
CA412565479 rs1466334476	82	G>V		No	ClinGen TOPMed
CA412565564 rs1337316450	86	I>M		No	ClinGen gnomAD
rs750631016 CA10367753	87	D>N		No	ClinGen ExAC TOPMed gnomAD
rs1273369343 CA412565579	87	D>V		No	ClinGen TOPMed gnomAD
rs1425520738 CA412565591	88	S>G		No	ClinGen TOPMed
CA412565737 rs1293533847	89	I>V		No	ClinGen gnomAD
TCGA novel	95	E>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10367764 rs770681620	100	L>F		No	ClinGen ExAC gnomAD
CA10367765 rs774131287	101	S>G		No	ClinGen ExAC TOPMed gnomAD
CA10367767 rs767100593	104	S>C		No	ClinGen ExAC TOPMed gnomAD
CA412566161 rs1406001764	107	R>Q		No	ClinGen TOPMed gnomAD
COSM1119231 rs746297985 CA10367771	107	R>W	Variant assessed as Somatic; 0.0 impact. endometrium [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC NCI-TCGA TOPMed gnomAD
TCGA novel	114	I>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs745477114 CA10367784	115	V>A		No	ClinGen ExAC gnomAD
TCGA novel	117	G>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1924581492 RCV001311824	117	G>V		No	ClinVar dbSNP
rs1365696466 CA412567127	119	A>T		No	ClinGen TOPMed
CA327512441 rs886995286	120	I>V		No	ClinGen TOPMed gnomAD
CA10367787 rs760532479	127	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
TCGA novel	128	D>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA412567196 rs1405277671	129	G>R		No	ClinGen gnomAD
CA412567213 rs1338534700	132	V>L		No	ClinGen gnomAD
rs1379607139 CA412567257	138	E>Q		No	ClinGen gnomAD
CA412567269 rs1390508524	139	V>A		No	ClinGen gnomAD
CA412567292 rs1318305388	143	E>K		No	ClinGen TOPMed gnomAD
CA412567293 rs1318305388	143	E>Q		No	ClinGen TOPMed gnomAD
TCGA novel	147	Y>H	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA345016 rs397515552	150	I>T		No	ClinGen Ensembl
rs764976472 CA10367791	153	L>V		No	ClinGen ExAC gnomAD
rs1322121662 CA412567387	156	K>R		No	ClinGen gnomAD
TCGA novel	162	L>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	173	S>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs965542541 CA327512495	176	A>V		No	ClinGen TOPMed
CA327512497 rs957265124	179	R>Q		No	ClinGen Ensembl
CA327512496 rs372123008	179	R>W		No	ClinGen ESP TOPMed gnomAD
TCGA novel	185	G>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA412568703 rs1168143614	185	G>S		No	ClinGen gnomAD
CA10367810 rs761690102	190	T>P		No	ClinGen ExAC gnomAD
CA412568755 rs1406267221	192	K>R		No	ClinGen gnomAD
rs1424274864 CA412568766	193	D>E		No	ClinGen TOPMed
rs1249705549 CA412568775	195	L>F		No	ClinGen TOPMed
CA327512500 rs986533987	204	I>V		No	ClinGen Ensembl
CA10367814 rs752838796	206	C>S		No	ClinGen ExAC gnomAD
rs1222075173 CA412568853	207	E>A		No	ClinGen gnomAD
CA10367815 rs760845233	208	I>T		No	ClinGen ExAC gnomAD
CA412568863 rs1490886759	209	V>I		No	ClinGen TOPMed gnomAD
CA412568864 rs1490886759	209	V>L		No	ClinGen TOPMed gnomAD
rs1485538098 CA412568887	212	K>N		No	ClinGen gnomAD
CA10367817 rs754390941	212	K>R		No	ClinGen ExAC gnomAD
rs779423576 CA10367819	217	T>A		No	ClinGen ExAC gnomAD
rs1465246800 CA412568959	221	I>V		No	ClinGen gnomAD
TCGA novel	222	D>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA247199 RCV000179890 rs794727866	233	M>I		No	ClinGen ClinVar Ensembl dbSNP
TCGA novel	237	C>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	238	G>D	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10367838 rs751238986	239	D>N		No	ClinGen ExAC gnomAD
CA412569124 rs1398482534	243	N>K		No	ClinGen gnomAD
TCGA novel	243	N>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	244	L>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10367839 rs754524227	244	L>I		No	ClinGen ExAC gnomAD
CA327512569 rs879048096	245	K>N		No	ClinGen Ensembl
TCGA novel	246	G>*	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	246	G>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs950063409 CA327512570	247	D>E		No	ClinGen Ensembl
CA10367840 rs199722252	250	Q>R		No	ClinGen 1000Genomes ExAC
TCGA novel	251	V>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10367858 rs767127871	259	V>I	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs1407368373 CA412570147	263	Y>C		No	ClinGen TOPMed
CA10367861 rs755650468	264	A>S		No	ClinGen ExAC gnomAD
CA10367860 rs755650468	264	A>T		No	ClinGen ExAC gnomAD
rs749234203 CA10367862	265	K>R		No	ClinGen ExAC gnomAD
rs973626241 CA327513100	266	E>D		No	ClinGen Ensembl
RCV000480904 CA16621304 rs1064794901	277	L>F		No	ClinGen ClinVar Ensembl dbSNP
rs1344938045 CA412570440	280	V>I		No	ClinGen gnomAD
rs1925184279 RCV001041036	282	I>V		No	ClinVar dbSNP
CA412570495 rs1281334383	284	T>P		No	ClinGen gnomAD
CA10367867 rs777026229	287	E>D		No	ClinGen ExAC gnomAD
TCGA novel	296	R>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA10367882 rs753356030	297	L>V		No	ClinGen ExAC gnomAD
rs1221405110 CA412570856	299	L>I		No	ClinGen TOPMed
CA327513152 rs994862471	303	M>V		No	ClinGen Ensembl
CA327513153 rs1055918181	305	V>A		No	ClinGen Ensembl
CA10367884 rs778763483	308	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA10367900 rs753505984	326	S>L		No	ClinGen ExAC gnomAD
rs940753056 CA327513816	327	L>I		No	ClinGen Ensembl
CA345018 rs397515553	328	Y>S		No	ClinGen Ensembl
TCGA novel	332	L>R	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA412571839 CA412571840 rs1200431087	333	G>R		No	ClinGen TOPMed
rs140572405 CA327513817	334	R>C		No	ClinGen ESP TOPMed gnomAD
rs199670083 CA10367902	334	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA412571847 rs199670083	334	R>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs375901202 CA10367903	337	C>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs780136285 CA10367904	338	P>S		No	ClinGen ExAC gnomAD
CA412571891 rs1317370713	341	F>Y		No	ClinGen TOPMed
CA10367907 rs749489883	345	I>M		No	ClinGen ExAC TOPMed gnomAD
CA327513818 rs184799167	346	V>I		No	ClinGen 1000Genomes ESP TOPMed gnomAD
CA10367909 rs778988971	347	C>S		No	ClinGen ExAC gnomAD
TCGA novel	354	L>F	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1224934092 CA412572187	359	T>A		No	ClinGen TOPMed
rs776987766 CA10367933	365	K>Q		No	ClinGen ExAC TOPMed gnomAD
rs200063268 CA10367934	367	P>L		No	ClinGen 1000Genomes ExAC gnomAD

1 associated diseases with P52788

[MIM: 309583]: Intellectual developmental disorder, X-linked, syndromic, Snyder-Robinson type (MRXSSR)

An X-linked intellectual disability syndrome characterized by a collection of clinical features including facial asymmetry, marfanoid habitus, hypertonia, osteoporosis and unsteady gait. {ECO:0000269|PubMed:14508504, ECO:0000269|PubMed:18550699, ECO:0000269|PubMed:19206178, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23696453, ECO:0000269|PubMed:23897707}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

An X-linked intellectual disability syndrome characterized by a collection of clinical features including facial asymmetry, marfanoid habitus, hypertonia, osteoporosis and unsteady gait. {ECO:0000269|PubMed:14508504, ECO:0000269|PubMed:18550699, ECO:0000269|PubMed:19206178, ECO:0000269|PubMed:22612257, ECO:0000269|PubMed:23696453, ECO:0000269|PubMed:23897707}. Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for P52788

Type	Name	Position	InterPro Accession
conserved_site	Polyamine biosynthesis domain, conserved site	194 - 207	IPR030373
domain	Polyamine biosynthesis domain	122 - 362	IPR030374
domain	Spermidine synthase, tetramerisation domain	123 - 172	IPR035246
domain	Spermine synthase, N-terminal	21 - 117	IPR040900

Functions

		Description
EC Number	2.5.1.22	Transferring alkyl or aryl groups, other than methyl groups
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

2 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.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.

1 GO annotations of molecular function

Name	Definition
spermine synthase activity	Catalysis of the reaction: S-adenosylmethioninamine + spermidine = 5'-methylthioadenosine + spermine.

3 GO annotations of biological process

Name	Definition
methionine metabolic process	The chemical reactions and pathways involving methionine (2-amino-4-(methylthio)butanoic acid), a sulfur-containing, essential amino acid found in peptide linkage in proteins.
polyamine metabolic process	The chemical reactions and pathways involving polyamines, any organic compound containing two or more amino groups.
spermine biosynthetic process	The chemical reactions and pathways resulting in the formation of spermine, a polybasic amine found in human sperm, in ribosomes and in some viruses and involved in nucleic acid packaging.

2 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q3SZA5	SMS	Spermine synthase	Bos taurus (Bovine)	PR
P97355	Sms	Spermine synthase	Mus musculus (Mouse)	PR

10	20	30	40	50	60
MAAARHSTLD	FMLGAKADGE	TILKGLQSIF	QEQGMAESVH	TWQDHGYLAT	YTNKNGSFAN
70	80	90	100	110	120
LRIYPHGLVL	LDLQSYDGDA	QGKEEIDSIL	NKVEERMKEL	SQDSTGRVKR	LPPIVRGGAI
130	140	150	160	170	180
DRYWPTADGR	LVEYDIDEVV	YDEDSPYQNI	KILHSKQFGN	ILILSGDVNL	AESDLAYTRA
190	200	210	220	230	240
IMGSGKEDYT	GKDVLILGGG	DGGILCEIVK	LKPKMVTMVE	IDQMVIDGCK	KYMRKTCGDV
250	260	270	280	290	300
LDNLKGDCYQ	VLIEDCIPVL	KRYAKEGREF	DYVINDLTAV	PISTSPEEDS	TWEFLRLILD
310	320	330	340	350	360
LSMKVLKQDG	KYFTQGNCVN	LTEALSLYEE	QLGRLYCPVE	FSKEIVCVPS	YLELWVFYTV

WKKAKP