AiPD: Autoinhibited Protein Database

P13073

Gene name	COX4I1 (COX4)
Protein name	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial
Names	Cytochrome c oxidase polypeptide IV, Cytochrome c oxidase subunit IV isoform 1, COX IV-1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:1327
EC number
Protein Class

Descriptions

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

Autoinhibitory domains (AIDs)

31-101 (Predicted disordered autoinhibitory region) PR

Target domain
Relief mechanism
Assay	cis-regPred

AID

31-101 (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

2 structures for P13073

Entry ID	Method	Resolution	Chain	Position	Source
5Z62	EM	360 A	D	26-169	PDB
AF-P13073-F1	Predicted				AlphaFoldDB

194 variants for P13073

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
VAR_084181 rs1906146144 RCV001034697	101	K>NS	Cytochrome-c oxidase deficiency disease MC4DN16; decreased COX4I1 protein levels [ClinVar, UniProt]	Yes	ClinVar dbSNP UniProt
RCV001034698 VAR_084182 rs1906247824	152	P>T	Mitochondrial complex 4 deficiency, nuclear type 16 MC4DN16 [ClinVar, UniProt]	Yes	ClinVar dbSNP UniProt
CA285735141 rs11557187	3	A>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
VAR_061127 rs11557187 CA8216480	3	A>T		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA396992075 rs1359855595	4	T>I		No	ClinGen gnomAD
CA396992079 rs1211604648	5	R>G		No	ClinGen TOPMed gnomAD
CA8216484 rs751801715	5	R>K		No	ClinGen ExAC gnomAD
rs537535282 CA285735171	5	R>S		No	ClinGen TOPMed
CA285735173 rs1041068718	6	V>A		No	ClinGen TOPMed
CA396992085 rs1450560903	6	V>L		No	ClinGen gnomAD
CA8216487 rs750534183	8	S>N		No	ClinGen ExAC gnomAD
CA396992099 rs750534183	8	S>T		No	ClinGen ExAC gnomAD
CA396992106 rs1343890788	9	L>P		No	ClinGen TOPMed
CA396992109 rs1389992958	10	V>L		No	ClinGen gnomAD
TCGA novel	14	A>T	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA8216489 rs780164636	15	I>V		No	ClinGen ExAC TOPMed gnomAD
CA285735215 rs749233847	16	S>C		No	ClinGen ExAC TOPMed gnomAD
rs749233847 CA8216490	16	S>F		No	ClinGen ExAC TOPMed gnomAD
rs1277010897 CA396992152	17	T>N		No	ClinGen TOPMed
CA396992149 rs1337848701	17	T>P		No	ClinGen TOPMed
rs1415977775 CA396992159	18	S>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	ClinGen NCI-TCGA TOPMed
rs142776923 CA8216494	19	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA8216495 rs202146194	22	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs1377221613 CA396992787	25	E>A		No	ClinGen gnomAD
rs957691740 CA285739200	25	E>D		No	ClinGen Ensembl
CA396992199 rs1297099654	25	E>Q		No	ClinGen gnomAD
CA8216521 rs147346083	26	S>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs139489638 CA8216522	26	S>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs1597218430 CA396992811	27	V>F		No	ClinGen Ensembl
rs1429089080 CA396992832	29	K>E		No	ClinGen gnomAD
CA396992849 rs1303659834	30	S>N		No	ClinGen gnomAD
CA8216525 rs373734689	30	S>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA285739214 rs771968237	31	E>K		No	ClinGen Ensembl
rs759454863 CA8216527	31	E>V		No	ClinGen ExAC
rs913801825 CA285739219	32	D>H		No	ClinGen gnomAD
CA396992873 rs913801825	32	D>N		No	ClinGen gnomAD
CA396992901 rs1326584155	33	F>L		No	ClinGen gnomAD
rs765105753 CA8216528	33	F>V		No	ClinGen ExAC gnomAD
rs1597218475 CA396992893	33	F>Y		No	ClinGen Ensembl
CA396992905 rs539978958	34	S>A		No	ClinGen 1000Genomes ExAC gnomAD
rs201058411 COSM1380271 CA8216530	34	S>L	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs539978958 CA8216529	34	S>P		No	ClinGen 1000Genomes ExAC gnomAD
rs201058411 CA285739235	34	S>W		No	ClinGen ExAC TOPMed gnomAD
CA396992911 rs1370750405	35	L>V		No	ClinGen TOPMed
CA396992940 rs1597218526	37	A>S		No	ClinGen Ensembl
rs932067795 CA285739276	37	A>V		No	ClinGen TOPMed
VAR_002170	38	Y>F		No	UniProt
CA285739277 rs11557185	38	Y>H		No	ClinGen TOPMed
CA8216535 CA396992973 COSM23302 rs745400280	39	M>I	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA8216534 rs780684895	39	M>L		No	ClinGen ExAC gnomAD
COSM1380272 CA396992962 rs780684895	39	M>V	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
TCGA novel	40	D>E	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA8216537 rs149461099	41	R>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA8216538 rs149461099	41	R>Q	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen 1000Genomes ESP ExAC NCI-TCGA TOPMed gnomAD
rs769159647 CA8216536	41	R>W		No	ClinGen ExAC gnomAD
CA8216539 rs772561167	42	R>C		No	ClinGen ExAC TOPMed gnomAD
CA8216540 rs772561167	42	R>G		No	ClinGen ExAC TOPMed gnomAD
CA8216541 rs201313443	42	R>H		No	ClinGen 1000Genomes ExAC gnomAD
rs771065408 CA8216542	43	D>E		No	ClinGen ExAC gnomAD
CA396993021 rs1597218579	44	H>Y		No	ClinGen Ensembl
CA396993036 rs770498990	45	P>L		No	ClinGen TOPMed
CA285739350 rs770498990	45	P>R		No	ClinGen TOPMed
rs759508701 CA8216546	45	P>S		No	ClinGen ExAC gnomAD
rs759508701 CA8216545	45	P>T		No	ClinGen ExAC gnomAD
CA8216547 rs775398027	47	P>L		No	ClinGen ExAC TOPMed gnomAD
CA396993076 rs1597218618	48	E>D		No	ClinGen Ensembl
rs991810828 CA285739379	49	V>G		No	ClinGen gnomAD
CA8216551 rs756860726	51	H>Y		No	ClinGen ExAC gnomAD
CA8216552 rs370929782	52	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA285739403 rs370929782	52	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1219983440 CA396993131	53	K>R		No	ClinGen TOPMed gnomAD
rs1219983440 CA396993130	53	K>T		No	ClinGen TOPMed gnomAD
rs1597218661 CA396993147	54	H>L		No	ClinGen Ensembl
rs1597218665 CA396993151	54	H>Q		No	ClinGen Ensembl
CA396993139 rs1567843670	54	H>Y		No	ClinGen Ensembl
CA285739411 rs773110239	60	K>E		No	ClinGen TOPMed gnomAD
rs1210861451 CA396993228	61	A>P		No	ClinGen TOPMed gnomAD
CA396993247 rs1464285613	62	L>F		No	ClinGen gnomAD
rs2599091 CA8216556	62	L>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA8216557 rs758991267	62	L>S		No	ClinGen ExAC
rs2599091 CA396993239	62	L>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA396993329 rs778220898	68	A>S		No	ClinGen ExAC
CA8216559 rs778220898	68	A>T		No	ClinGen ExAC
rs1182164590 CA396993339	69	S>A		No	ClinGen gnomAD
rs1567843713	69	S>missing	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	NCI-TCGA
CA396993341 rs1597218718	69	S>Y		No	ClinGen Ensembl
CA285739451 rs1048702246	70	W>*		No	ClinGen Ensembl
rs1184725448 CA396993349	70	W>R		No	ClinGen TOPMed
CA8216562 rs771139213	71	S>N		No	ClinGen ExAC gnomAD
CA8216560 rs747411276	71	S>R		No	ClinGen ExAC TOPMed gnomAD
rs771139213 CA8216561	71	S>T		No	ClinGen ExAC gnomAD
rs887346101 CA285739468	72	S>T		No	ClinGen Ensembl
CA396993378 rs1163949863	73	L>F		No	ClinGen gnomAD
CA285739474 rs368486192	74	S>A		No	ClinGen Ensembl
CA396993391 rs376218422	75	M>R		No	ClinGen ESP ExAC gnomAD
rs376218422 CA8216565	75	M>T		No	ClinGen ESP ExAC gnomAD
CA8216564 rs561331286	75	M>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA8216568 rs764048670 CA8216567	77	E>D		No	ClinGen ExAC TOPMed gnomAD
rs1271285129 CA396993419	79	V>L		No	ClinGen TOPMed
CA8216570 rs142400268 CA8216571	80	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA8216569 rs761492668	80	E>K	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA gnomAD
rs761492668 CA396993424	80	E>Q		No	ClinGen ExAC gnomAD
rs781343693 CA8216598	81	L>S		No	ClinGen ExAC gnomAD
CA8216600 rs756239305	83	R>C		No	ClinGen ExAC TOPMed gnomAD
rs374125919 CA8216601	83	R>H	Variant assessed as Somatic; 4.619e-05 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
rs749552922 CA8216602	84	I>V		No	ClinGen ExAC TOPMed gnomAD
CA396993545 rs1437212215	85	K>T		No	ClinGen gnomAD
rs1276833253 CA396993592	88	E>D		No	ClinGen gnomAD
rs1185957235 CA396993598	89	S>G		No	ClinGen TOPMed gnomAD
CA396993684 rs1233820692	95	R>M		No	ClinGen TOPMed gnomAD
TCGA novel	96	G>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA8216606 rs367714586	97	S>L		No	ClinGen 1000Genomes ESP ExAC gnomAD
rs562155866 CA8216604	97	S>P		No	ClinGen 1000Genomes ExAC gnomAD
rs562155866 CA396993704	97	S>T		No	ClinGen 1000Genomes ExAC gnomAD
rs367714586 CA8216605	97	S>W		No	ClinGen 1000Genomes ESP ExAC gnomAD
CA396993718 rs1451693526	98	N>Y		No	ClinGen gnomAD
CA8216609 rs770901016	102	T>M		No	ClinGen ExAC TOPMed gnomAD
CA396993785 rs770901016	102	T>R		No	ClinGen ExAC TOPMed gnomAD
rs1167944509 CA396993781	102	T>S		No	ClinGen TOPMed
CA8216613 rs774898740	106	G>S		No	ClinGen ExAC TOPMed gnomAD
CA285740224 rs908619616	108	M>I		No	ClinGen TOPMed
rs768090930 CA8216615	108	M>V		No	ClinGen ExAC gnomAD
rs11557189 CA285740237	109	F>L		No	ClinGen Ensembl
CA396993893 rs371834112	111	I>F		No	ClinGen ESP ExAC TOPMed gnomAD
CA396993897 rs1348177297	111	I>T		No	ClinGen gnomAD
rs371834112 CA8216616	111	I>V	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ESP ExAC NCI-TCGA TOPMed gnomAD
CA8216618 rs146862566	112	G>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA8216619 rs146862566	112	G>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA285740252 rs772180664 COSM265687	115	A>T	Variant assessed as Somatic; 0.0 impact. large_intestine [NCI-TCGA, Cosmic]	No	ClinGen cosmic curated NCI-TCGA TOPMed gnomAD
CA8216621 rs375895416 COSM197384	115	A>V	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs758224726 CA8216623	116	L>F		No	ClinGen ExAC gnomAD
rs1229949005 CA396993960	116	L>P		No	ClinGen gnomAD
rs1803313 CA285740299	117	V>A		No	ClinGen Ensembl
rs746963034 CA396993966	117	V>F		No	ClinGen ExAC TOPMed gnomAD
CA8216625 rs746963034	117	V>I		No	ClinGen ExAC TOPMed gnomAD
CA396993982 rs11557184	118	I>M		No	ClinGen gnomAD
CA8216626 rs770833137	118	I>T		No	ClinGen ExAC TOPMed gnomAD
rs745444271 CA8216628 CA396993996 CA396993994	119	M>I		No	ClinGen ExAC TOPMed gnomAD
CA8216627 rs1803312	119	M>L		No	ClinGen ExAC gnomAD
rs11557188 CA285740341	122	K>E		No	ClinGen Ensembl
TCGA novel	124	Y>C	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA285740348 rs939018146	124	Y>F		No	ClinGen TOPMed
CA396994416 rs1355270986	126	Y>C		No	ClinGen TOPMed
rs751718635 CA8216665	127	G>S		No	ClinGen ExAC TOPMed gnomAD
rs968339586 CA396994440	128	P>A		No	ClinGen gnomAD
rs1374000211 CA396994445	128	P>L		No	ClinGen TOPMed
rs968339586 CA285741183	128	P>S		No	ClinGen gnomAD
rs1309190932 CA396994447	129	L>I		No	ClinGen TOPMed
TCGA novel	129	L>P	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
CA8216668 rs750425972	129	L>P		No	ClinGen ExAC gnomAD
TCGA novel	129	L>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1212074274 CA396994465	130	P>L		No	ClinGen TOPMed gnomAD
rs1465183753 CA396994477	131	Q>P		No	ClinGen TOPMed gnomAD
CA396994479 rs1465183753	131	Q>R		No	ClinGen TOPMed gnomAD
CA8216671 rs748913859	132	S>T		No	ClinGen ExAC TOPMed
rs1000212372 CA396994539	136	E>K		No	ClinGen TOPMed
rs1000212372 CA285741214	136	E>Q		No	ClinGen TOPMed
rs1427902927 CA396994563	137	W>C		No	ClinGen gnomAD
rs778356222 CA8216673	137	W>S		No	ClinGen ExAC TOPMed gnomAD
CA396994566 rs1165361356	138	V>L		No	ClinGen TOPMed gnomAD
rs1165361356 CA396994568	138	V>M		No	ClinGen TOPMed gnomAD
rs1597220655 CA396994583	139	A>G		No	ClinGen Ensembl
CA285741246 rs779219247	140	K>M		No	ClinGen ExAC gnomAD
rs747683244 CA8216674	140	K>Q		No	ClinGen ExAC gnomAD
CA8216675 rs779219247	140	K>R		No	ClinGen ExAC gnomAD
rs777096470 CA8216676	141	Q>E		No	ClinGen ExAC gnomAD
rs760105911 CA8216677	141	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA8216678 rs770133953	142	T>S		No	ClinGen ExAC gnomAD
rs144333119 CA8216679	143	K>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA8216680 rs146582440	145	M>I		No	ClinGen ESP ExAC gnomAD
CA285741283 rs980080098	145	M>L		No	ClinGen TOPMed
rs1803314 CA285741287	145	M>T		No	ClinGen Ensembl
CA396994667 rs1303407874	146	L>R		No	ClinGen gnomAD
rs1196534134 CA396994688	148	M>V		No	ClinGen TOPMed
rs1597220745 CA396994719	150	V>G		No	ClinGen Ensembl
CA8216682 rs751877897	150	V>L		No	ClinGen ExAC
rs761951269 CA8216683	152	P>R		No	ClinGen ExAC TOPMed gnomAD
rs767772859 CA8216684	156	L>F		No	ClinGen ExAC gnomAD
CA396994762 rs1597220799	157	A>S		No	ClinGen Ensembl
TCGA novel	157	A>V	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs1597220805 CA396994766	158	S>A		No	ClinGen Ensembl
rs577618111 CA8216685	158	S>C		No	ClinGen 1000Genomes ExAC gnomAD
rs1350871107 COSM346459 CA396994797	162	Y>H	lung [Cosmic]	No	ClinGen cosmic curated TOPMed
CA396994809 rs1370412304	163	E>D		No	ClinGen TOPMed
CA8216687 rs779831701	163	E>K	Variant assessed as Somatic; 0.0 impact. [NCI-TCGA]	No	ClinGen ExAC NCI-TCGA TOPMed gnomAD
rs1597220856 CA396994808	163	E>V		No	ClinGen Ensembl
TCGA novel	164	K>N	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs753608262 CA8216688	165	N>D		No	ClinGen ExAC gnomAD
CA8216689 rs754611348	165	N>K		No	ClinGen ExAC TOPMed gnomAD
TCGA novel	165	N>S	Variant assessed as Somatic; impact. [NCI-TCGA]	No	NCI-TCGA
rs777325740 CA8216693	166	E>D		No	ClinGen ExAC gnomAD
rs560428992 CA8216691	166	E>K		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA8216692 rs560428992	166	E>Q		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1412032777 CA396994836	167	W>*		No	ClinGen gnomAD

1 associated diseases with P13073

[MIM: 619060]: Mitochondrial complex IV deficiency, nuclear type 16 (MC4DN16)

An autosomal recessive mitochondrial disorder with onset in infancy and variable manifestations. MC4DN16 features include feeding difficulties, poor overall growth, short stature, microcephaly, developmental regression, severe hypotonia, and seizures. Cerebral and cerebellar atrophy, and abnormal lesions in the basal ganglia can be observed on brain imaging. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. {ECO:0000269|PubMed:28766551, ECO:0000269|PubMed:31290619}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

An autosomal recessive mitochondrial disorder with onset in infancy and variable manifestations. MC4DN16 features include feeding difficulties, poor overall growth, short stature, microcephaly, developmental regression, severe hypotonia, and seizures. Cerebral and cerebellar atrophy, and abnormal lesions in the basal ganglia can be observed on brain imaging. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV. {ECO:0000269|PubMed:28766551, ECO:0000269|PubMed:31290619}. Note=The disease is caused by variants affecting the gene represented in this entry.

No regional properties for P13073

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for P13073

Functions

		Description
EC Number
Subcellular Localization	Mitochondrion inner membrane ; Single-pass membrane protein
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

8 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.
integral component of membrane	The component of a membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
mitochondrial inner membrane	The inner, i.e. lumen-facing, lipid bilayer of the mitochondrial envelope. It is highly folded to form cristae.
mitochondrial membrane	Either of the lipid bilayers that surround the mitochondrion and form the mitochondrial envelope.
mitochondrial respiratory chain complex IV	A protein complex located in the mitochondrial inner membrane that forms part of the mitochondrial respiratory chain. Contains the 13 polypeptide subunits of cytochrome c oxidase, including cytochrome a and cytochrome a3. Catalyzes the oxidation of reduced cytochrome c by dioxygen (O2).
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.

1 GO annotations of molecular function

Name	Definition
cytochrome-c oxidase activity	Catalysis of the reaction: 4 ferrocytochrome c + O2 + 4 H+ = 4 ferricytochrome c + 2 H2O.

3 GO annotations of biological process

Name	Definition
cellular respiration	The enzymatic release of energy from inorganic and organic compounds (especially carbohydrates and fats) which either requires oxygen (aerobic respiration) or does not (anaerobic respiration).
generation of precursor metabolites and energy	The chemical reactions and pathways resulting in the formation of precursor metabolites, substances from which energy is derived, and any process involved in the liberation of energy from these substances.
mitochondrial electron transport, cytochrome c to oxygen	The transfer of electrons from cytochrome c to oxygen that occurs during oxidative phosphorylation, mediated by the multisubunit enzyme known as complex IV.

No homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
No homologous proteins

10	20	30	40	50	60
MLATRVFSLV	GKRAISTSVC	VRAHESVVKS	EDFSLPAYMD	RRDHPLPEVA	HVKHLSASQK
70	80	90	100	110	120
ALKEKEKASW	SSLSMDEKVE	LYRIKFKESF	AEMNRGSNEW	KTVVGGAMFF	IGFTALVIMW
130	140	150	160
QKHYVYGPLP	QSFDKEWVAK	QTKRMLDMKV	NPIQGLASKW	DYEKNEWKK