AiPD: Autoinhibited Protein Database

Q8NI22

Gene name	MCFD2 (SDNSF)
Protein name	Multiple coagulation factor deficiency protein 2
Names	Neural stem cell-derived neuronal survival protein
Species	Homo sapiens (Human)
KEGG Pathway	hsa:90411
EC number
Protein Class

Descriptions

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

Autoinhibitory domains (AIDs)

1-72 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

1-72 (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

11 structures for Q8NI22

Entry ID	Method	Resolution	Chain	Position	Source
2VRG	NMR	-	A	27-146	PDB
3A4U	X-ray	184 A	B	27-146	PDB
3LCP	X-ray	245 A	C/D	58-146	PDB
3WHT	X-ray	180 A	B	67-146	PDB
3WHU	X-ray	260 A	B	67-146	PDB
3WNX	X-ray	275 A	B	67-146	PDB
4YGB	X-ray	160 A	B/D	67-146	PDB
4YGC	X-ray	240 A	B/D/F/H	67-146	PDB
4YGD	X-ray	251 A	B/D/F/H	67-146	PDB
4YGE	X-ray	305 A	B/D/F	27-146	PDB
AF-Q8NI22-F1	Predicted				AlphaFoldDB

158 variants for Q8NI22

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
RCV000985001 rs1572611822 CA346712610	16	L>P	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000003001 rs1253799389	35	Q>missing	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinVar dbSNP
rs756021929 RCV000316889 CA10613552	36	P>A	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000294495 CA10615717 rs886056118	79	M>T	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs78289603 CA46626204 VAR_072245	81	D>H	F5F8D2 [UniProt]	Yes	ClinGen UniProt Ensembl dbSNP
rs78289603 RCV000003006 CA115804	81	D>Y	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
RCV000003002 rs1294221028 RCV001580061	83	D>missing	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinVar dbSNP
rs1558461545 RCV000003003	89	D>missing	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinVar dbSNP
CA1646858 rs768388209 RCV001137002	121	I>M	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
RCV000851982 rs1484184249	127	D>missing	Factor V and factor VIII, combined deficiency of, type 1 [ClinVar]	Yes	ClinVar dbSNP
VAR_019076 CA115788 RCV000003004 rs137852913	129	D>E	Factor 5 and Factor VIII, combined deficiency of, 2 F5F8D2; interferes with protein folding [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt Ensembl dbSNP
rs748641905 CA1646850 VAR_072246	135	Y>N	F5F8D2 [UniProt]	Yes	ClinGen UniProt ExAC dbSNP gnomAD
rs137852914 CA115796 VAR_019077 RCV000003005	136	I>T	Factor 5 and Factor VIII, combined deficiency of, 2 F5F8D2; interferes with protein folding [ClinVar, UniProt]	Yes	ClinGen ClinVar UniProt ExAC dbSNP
rs80294301 CA1646840 RCV000330681 RCV001270570	139	A>V	Factor 5 and Factor VIII, combined deficiency of, 2 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA346712689 rs1254106218	3	M>T		No	ClinGen gnomAD
rs900041651 CA46626922	3	M>V		No	ClinGen TOPMed gnomAD
rs777983162 CA1646986	5	S>F		No	ClinGen ExAC gnomAD
CA346712674 rs777983162	5	S>Y		No	ClinGen ExAC gnomAD
CA1646985 rs371098791	6	L>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1297497901 CA346712671	6	L>V		No	ClinGen gnomAD
rs1454584927 CA346712658	8	R>S		No	ClinGen gnomAD
CA1646982 rs755090937	8	R>T		No	ClinGen ExAC gnomAD
rs1005839493 CA46626903	9	T>I		No	ClinGen TOPMed
CA346712653 rs1005839493	9	T>N		No	ClinGen TOPMed
CA346712655 rs1572611879	9	T>P		No	ClinGen Ensembl
CA346712648 rs1172452105	10	P>H		No	ClinGen TOPMed gnomAD
CA346712646 rs1172452105	10	P>L		No	ClinGen TOPMed gnomAD
CA346712631 rs1375324203	13	C>R		No	ClinGen TOPMed gnomAD
rs11555002 CA46626889	14	G>C		No	ClinGen gnomAD
CA346712624 rs11555002	14	G>S		No	ClinGen gnomAD
CA346712602 rs1183830132	17	W>C		No	ClinGen gnomAD
CA1646977 rs767223303	17	W>S		No	ClinGen ExAC gnomAD
CA346712590 rs1176879847	19	F>S		No	ClinGen TOPMed
rs1163253991 CA346712577	21	A>T		No	ClinGen gnomAD
rs768254017 COSM575540 CA1646974	22	P>L	lung Variant assessed as Somatic; 0.0 impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated ExAC NCI-TCGA gnomAD
CA1646975 rs773962348	22	P>S		No	ClinGen ExAC
rs777188077 CA1646972	23	G>S		No	ClinGen ExAC gnomAD
rs937344425 CA46626860	24	A>D		No	ClinGen Ensembl
CA346712563 rs747338625	24	A>P		No	ClinGen ExAC TOPMed gnomAD
rs747338625 CA1646970	24	A>T	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
TCGA novel	24	A>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA1646969 rs201005763	25	R>G		No	ClinGen 1000Genomes ExAC gnomAD
rs1248468378 CA346712550	26	A>G		No	ClinGen gnomAD
rs1338731005 CA346712540	27	E>D		No	ClinGen gnomAD
rs772241915 CA1646968	28	E>*		No	ClinGen ExAC TOPMed gnomAD
rs772241915 CA46626852	28	E>Q		No	ClinGen ExAC TOPMed gnomAD
rs1392087938 CA346712530	29	P>R		No	ClinGen TOPMed gnomAD
CA46626843 rs927338670	29	P>S		No	ClinGen TOPMed
CA46626846 rs927338670	29	P>T		No	ClinGen TOPMed
rs879024913 CA46626837	30	A>G		No	ClinGen TOPMed gnomAD
rs748338168 CA1646967	30	A>T		No	ClinGen ExAC gnomAD
rs1429442154 CA346712525	31	A>P		No	ClinGen gnomAD
CA346712519 rs1386263684	32	S>G		No	ClinGen gnomAD
CA1646966 rs779155851	32	S>I		No	ClinGen ExAC gnomAD
CA346712510 rs1366396078	33	F>V		No	ClinGen gnomAD
CA1646964 rs749396379	34	S>F		No	ClinGen ExAC gnomAD
rs376476823 CA346712493	35	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs756021929 CA1646962	36	P>S		No	ClinGen ExAC TOPMed gnomAD
rs201137824 CA46626814	37	G>S		No	ClinGen 1000Genomes TOPMed
rs1462774767 CA346712479	38	S>N		No	ClinGen TOPMed
rs757163409 CA1646958	39	M>L		No	ClinGen ExAC TOPMed gnomAD
CA46626808 rs757163409	39	M>V		No	ClinGen ExAC TOPMed gnomAD
CA346712467 rs1450160438	40	G>S		No	ClinGen TOPMed
rs1188837024 CA346712459	41	L>P		No	ClinGen TOPMed
rs141927904 CA1646957	42	D>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA1646956 rs763902751	43	K>E		No	ClinGen ExAC gnomAD
rs534474434 CA46626787	44	N>S		No	ClinGen 1000Genomes TOPMed gnomAD
rs762456312 CA1646955	45	T>I		No	ClinGen ExAC TOPMed gnomAD
CA1646953 rs774875101	46	V>A		No	ClinGen ExAC gnomAD
rs761116621 CA1646951	47	H>D		No	ClinGen ExAC gnomAD
rs778325740 CA1646950	47	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA346712412 rs1470147097	48	D>E		No	ClinGen gnomAD
rs1162286700 COSM1532215 CA346712418	48	D>H	lung Variant assessed as Somatic; 0.0 impact. [Cosmic, NCI-TCGA]	No	ClinGen cosmic curated NCI-TCGA TOPMed gnomAD
CA346712419 rs1162286700	48	D>N	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed gnomAD
rs369431266 CA1646947	50	E>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs1436617131 CA346712401	50	E>K		No	ClinGen TOPMed
CA346712378 rs1558461744	51	H>L		No	ClinGen Ensembl
rs775825745 CA1646926	52	I>M		No	ClinGen ExAC TOPMed gnomAD
rs558502042 CA1646925	53	M>I		No	ClinGen 1000Genomes ExAC gnomAD
CA346712355 rs1325851793	54	E>D		No	ClinGen TOPMed
CA46626262 rs543577609	54	E>Q		No	ClinGen 1000Genomes
CA1646924 rs746007921	57	E>D		No	ClinGen ExAC gnomAD
rs1221772963 CA346712337	57	E>G		No	ClinGen TOPMed
rs192820723 CA1646923	59	V>A		No	ClinGen 1000Genomes ExAC gnomAD
CA1646922 rs771003004	61	N>H		No	ClinGen ExAC gnomAD
CA1646921 rs138519672	61	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA1646919 rs777741288	63	P>S		No	ClinGen ExAC gnomAD
rs914718297 CA46626248	64	E>Q		No	ClinGen gnomAD
CA346712286 rs200415122	65	A>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs200415122 CA1646918	65	A>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1646916 rs778684574	66	E>D		No	ClinGen ExAC gnomAD
TCGA novel	66	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1412721285 CA346712284	66	E>Q		No	ClinGen TOPMed gnomAD
COSM3426483 CA1646915 rs754442571	68	S>L	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
CA46626234 rs535874558	69	P>S		No	ClinGen 1000Genomes
rs137964402 CA1646911	73	Q>*		No	ClinGen ESP ExAC TOPMed gnomAD
CA346712235 rs137964402	73	Q>E		No	ClinGen ESP ExAC TOPMed gnomAD
rs1239316807 CA346712226	74	L>H		No	ClinGen TOPMed gnomAD
rs1239316807 CA346712225	74	L>P		No	ClinGen TOPMed gnomAD
CA346712184 rs1156867409	77	F>Y		No	ClinGen TOPMed
rs764322613 CA1646908	79	M>I		No	ClinGen ExAC gnomAD
rs751887064 CA1646909	79	M>L		No	ClinGen ExAC gnomAD
CA346712127 rs763394078	80	H>D		No	ClinGen ExAC gnomAD
rs763394078 CA1646907	80	H>Y		No	ClinGen ExAC gnomAD
CA346712093 rs1294877068	82	Y>C		No	ClinGen gnomAD
rs1359783243 CA346712048	85	N>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
rs775513362 CA346712006	88	L>P		No	ClinGen ExAC gnomAD
rs775513362 CA1646906	88	L>R		No	ClinGen ExAC gnomAD
CA346712014 rs1458296838	88	L>V		No	ClinGen gnomAD
rs994703366 CA46626189	90	G>A		No	ClinGen TOPMed
CA346711980 rs994703366	90	G>D		No	ClinGen TOPMed
rs1379217647 CA346711985	90	G>S		No	ClinGen gnomAD
CA346711968 rs1304048981	91	L>F		No	ClinGen gnomAD
CA346711952 rs1572609626	92	E>D		No	ClinGen Ensembl
rs1445238415 CA346711944	93	L>F		No	ClinGen gnomAD
CA1646905 rs770123754	95	T>I		No	ClinGen ExAC gnomAD
rs759679044 CA1646904	96	A>V		No	ClinGen ExAC TOPMed gnomAD
rs1572609585 CA346711877	99	H>D		No	ClinGen Ensembl
rs79211648 CA46626171	100	V>D		No	ClinGen Ensembl
CA1646901 rs746904307	101	H>P		No	ClinGen ExAC TOPMed gnomAD
rs746904307 CA1646902	101	H>R	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs1168152311 CA346711850	101	H>Y		No	ClinGen gnomAD
CA346710858 rs1175457096	106	S>N		No	ClinGen gnomAD
rs1366185198 CA346710852	106	S>R		No	ClinGen gnomAD
CA46624849 rs950948431	109	A>T		No	ClinGen TOPMed gnomAD
CA46624843 rs373893031	111	L>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs765195770 CA46624837	111	L>P		No	ClinGen Ensembl
rs373893031 CA46624845	111	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
TCGA novel rs1467999949 CA346710782	112	M>I	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen gnomAD NCI-TCGA
CA1646863 rs370788387	112	M>T		No	ClinGen ESP ExAC gnomAD
rs141584198 CA1646862	114	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs767334331 CA1646861	115	D>G		No	ClinGen ExAC gnomAD
TCGA novel	116	E>K	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1199851863 CA346710717	117	L>V		No	ClinGen TOPMed
rs199922892 CA1646860	118	I>T		No	ClinGen ExAC TOPMed gnomAD
CA1646859 rs774183668	120	I>L		No	ClinGen ExAC gnomAD
rs774183668 CA46624801	120	I>V		No	ClinGen ExAC gnomAD
TCGA novel	121	I>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
RCV001270559 rs1668185105	122	D>N		No	ClinVar dbSNP
rs775052308 CA1646856	123	G>C		No	ClinGen ExAC TOPMed gnomAD
rs1257293550 CA346710601	125	L>F		No	ClinGen TOPMed
CA46624793 rs967209929	125	L>M		No	ClinGen gnomAD
rs769498395 CA1646855	128	D>E		No	ClinGen ExAC
TCGA novel	129	D>G	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
TCGA novel	129	D>Y	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA46624784 rs201153154	132	N>D		No	ClinGen 1000Genomes
CA1646854 rs745351183	132	N>S		No	ClinGen ExAC TOPMed gnomAD
CA1646851 rs747447570	135	Y>L		No	ClinGen ExAC gnomAD
CA1646848 rs779577150	136	I>V		No	ClinGen ExAC gnomAD
TCGA novel	137	D>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs80294301 CA1646841	139	A>D		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs148748272 CA1646843	139	A>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs148748272 CA1646842	139	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs761817833 CA1646839	142	A>G		No	ClinGen ExAC gnomAD
rs868709713 CA46624723	142	A>T		No	ClinGen Ensembl
rs764018345 CA1646837	146	Q>H		No	ClinGen ExAC TOPMed gnomAD
CA46624709 rs765992456	146	Q>K		No	ClinGen TOPMed gnomAD
rs751451785 CA1646838	146	Q>R		No	ClinGen ExAC gnomAD

1 associated diseases with Q8NI22

[MIM: 613625]: Factor V and factor VIII combined deficiency 2 (F5F8D2)

A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal. {ECO:0000269|PubMed:12717434, ECO:0000269|PubMed:18590741, ECO:0000269|PubMed:18685427, ECO:0000269|PubMed:20491958}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal. {ECO:0000269|PubMed:12717434, ECO:0000269|PubMed:18590741, ECO:0000269|PubMed:18685427, ECO:0000269|PubMed:20491958}. Note=The disease is caused by variants affecting the gene represented in this entry.

1 regional properties for Q8NI22

Type	Name	Position	InterPro Accession
domain	Synaptotagmin-like mitochondrial-lipid-binding domain	1 - 195	IPR031468

Functions

		Description
EC Number
Subcellular Localization	Endoplasmic reticulum-Golgi intermediate compartment Endoplasmic reticulum Golgi apparatus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
endoplasmic reticulum membrane	The lipid bilayer surrounding the endoplasmic reticulum.
endoplasmic reticulum-Golgi intermediate compartment membrane	The lipid bilayer surrounding any of the compartments of the endoplasmic reticulum (ER)-Golgi intermediate compartment system.
ER to Golgi transport vesicle membrane	The lipid bilayer surrounding a vesicle transporting substances from the endoplasmic reticulum to the Golgi.
Golgi apparatus	A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.

1 GO annotations of molecular function

Name	Definition
calcium ion binding	Binding to a calcium ion (Ca2+).

2 GO annotations of biological process

Name	Definition
protein transport	The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
vesicle-mediated transport	A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The process begins with a step that directs a substance to the forming vesicle, and includes vesicle budding and coating. Vesicles are then targeted to, and fuse with, an acceptor membrane.

2 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q8K5B2	Mcfd2	Multiple coagulation factor deficiency protein 2 homolog	Mus musculus (Mouse)	PR
Q8K5B3	Mcfd2	Multiple coagulation factor deficiency protein 2 homolog	Rattus norvegicus (Rat)	PR

10	20	30	40	50	60
MTMRSLLRTP	FLCGLLWAFC	APGARAEEPA	ASFSQPGSMG	LDKNTVHDQE	HIMEHLEGVI
70	80	90	100	110	120
NKPEAEMSPQ	ELQLHYFKMH	DYDGNNLLDG	LELSTAITHV	HKEEGSEQAP	LMSEDELINI
130	140
IDGVLRDDDK	NNDGYIDYAE	FAKSLQ