AiPD: Autoinhibited Protein Database

O95376

Gene name	ARIH2 (ARI2, TRIAD1)
Protein name	E3 ubiquitin-protein ligase ARIH2
Names	ARI-2, Protein ariadne-2 homolog, RING-type E3 ubiquitin transferase ARIH2, Triad1 protein
Species	Homo sapiens (Human)
KEGG Pathway	hsa:10425
EC number	2.3.2.31: Aminoacyltransferases
Protein Class	RBR FAMILY RING FINGER AND IBR DOMAIN-CONTAINING (PTHR11685)

Descriptions

E3 ubiquitin-protein ligase ARIH2 catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 and acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex and initiating ubiquitination of ECS substrates. ARIH2 is autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity. Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity.

Autoinhibitory domains (AIDs)

Target domain	300-340 (RING2 domain)
Relief mechanism	Partner binding
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

353-470 (Ariadne domain)

Target domain

300-340 (RING2 domain)

Relief mechanism

Partner binding (Binding of neddlyated CUL1-RBX1 to Ariadne domain)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Kelsall IR et al. (2013) "TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes", The EMBO journal, 32, 2848-60

Kostrhon S et al. (2021) "CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation", Nature chemical biology, 17, 1075-1083

Autoinhibited structure

Activated structure

3 structures for O95376

Entry ID	Method	Resolution	Chain	Position	Source
7OD1	X-ray	245 A	A/B	1-493	PDB
7ONI	EM	340 A	H	1-493	PDB
AF-O95376-F1	Predicted				AlphaFoldDB

181 variants for O95376

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs146714746 CA2387764	5	M>V		No	ClinGen ESP ExAC gnomAD
CA2387765 rs775296209	6	N>S		No	ClinGen ExAC TOPMed gnomAD
CA352648771 rs1251780705	10	S>A		No	ClinGen gnomAD
rs1251780705 CA352648749	10	S>P		No	ClinGen gnomAD
CA352648816 rs1338674813	11	D>G		No	ClinGen TOPMed gnomAD
rs768674285 CA2387767	12	S>N		No	ClinGen ExAC gnomAD
rs776299644 CA2387768	13	N>S		No	ClinGen ExAC gnomAD
rs200421825 CA73983302	16	D>Y		No	ClinGen 1000Genomes
rs1188970482 CA352649135	17	Y>C		No	ClinGen TOPMed gnomAD
CA2387769 rs138105757	18	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA352649235 rs1172945432	21	C>R		No	ClinGen gnomAD
rs1553695679 CA2387771	21	C>W		No	ClinGen Ensembl
rs11507 VAR_054105 CA73983339	24	E>K		No	ClinGen UniProt Ensembl dbSNP
rs762611632 CA2387777	28	E>D		No	ClinGen ExAC gnomAD
VAR_054106 rs34221642 CA2387778	29	E>D		No	ClinGen UniProt 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA73983389 rs753068638	30	D>E		No	ClinGen ExAC TOPMed gnomAD
rs772777170 CA352649684	31	D>H		No	ClinGen gnomAD
rs772777170 CA73983395	31	D>N		No	ClinGen gnomAD
rs150747484 CA2387782	32	P>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA2387783 rs754314513	32	P>L		No	ClinGen ExAC gnomAD
CA2387784 COSM1045973 rs757397436	37	D>N	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA73983440 rs1021548669	40	V>M		No	ClinGen Ensembl
CA352650167 rs1348383417	44	S>G		No	ClinGen gnomAD
CA2387786 rs746090221	44	S>N		No	ClinGen ExAC TOPMed gnomAD
rs746090221 CA352650168	44	S>T		No	ClinGen ExAC TOPMed gnomAD
rs1186750262 CA352650251	47	E>G		No	ClinGen TOPMed
rs977408244 CA73983479	50	G>A		No	ClinGen gnomAD
rs779744288 CA2387788	50	G>W		No	ClinGen ExAC gnomAD
CA73983495 rs112345459	57	E>D		No	ClinGen ExAC TOPMed gnomAD
rs1191734093 CA352650559	57	E>K		No	ClinGen gnomAD
rs776747405 CA2387791	58	E>D		No	ClinGen ExAC gnomAD
CA73983512 rs201971966	61	F>L		No	ClinGen 1000Genomes
CA352650717 rs200385612	62	T>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs200385612 CA2387792	62	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA2387794 rs772714830	66	Y>C		No	ClinGen ExAC gnomAD
rs1559717167 CA352650831	67	K>Q		No	ClinGen Ensembl
rs762547621 CA2387795	67	K>R		No	ClinGen ExAC gnomAD
CA2387796 rs766011857	68	E>D		No	ClinGen ExAC gnomAD
CA2387798 rs761068678	74	N>S		No	ClinGen ExAC gnomAD
rs1371680328 CA352651129	77	M>V		No	ClinGen TOPMed gnomAD
CA2387799 rs199731867	79	S>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA352651325 rs1218289551	85	K>N		No	ClinGen gnomAD
rs1285107929 CA352664703	88	H>L		No	ClinGen gnomAD
rs777806461 CA2387836	88	H>Y		No	ClinGen ExAC gnomAD
rs368954794 CA2387837	90	V>I		No	ClinGen ESP ExAC gnomAD
rs1208090185 CA352664768	91	A>T		No	ClinGen TOPMed gnomAD
rs1044557813 CA74007509	94	I>M		No	ClinGen Ensembl
rs770534282 CA2387838	94	I>V		No	ClinGen ExAC TOPMed gnomAD
CA352664997 rs1185909845	97	N>S		No	ClinGen gnomAD
CA352665077 rs1268185468	99	H>Y		No	ClinGen TOPMed
CA352665172 rs1455390747	101	Q>E		No	ClinGen TOPMed gnomAD
rs778423872 CA2387859	112	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1443845395 CA352666751	114	A>V		No	ClinGen gnomAD
rs757880723 CA2387861	116	L>V		No	ClinGen ExAC gnomAD
CA74009687 rs1042764160	117	L>F		No	ClinGen Ensembl
CA74009691 rs904255797	117	L>R		No	ClinGen Ensembl
rs527850935 CA2387862	118	V>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs527850935 CA352666847	118	V>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA2387863 rs746633869	119	E>D		No	ClinGen ExAC gnomAD
rs112979690 CA2387864	121	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs773388389 CA2387865	121	R>Q		No	ClinGen ExAC gnomAD
CA352667017 rs1576443772	122	V>G		No	ClinGen Ensembl
rs749836106 CA2387866	124	P>A		No	ClinGen ExAC gnomAD
rs377679410 CA2387867	125	N>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1576443875 CA352667172	128	K>E		No	ClinGen Ensembl
rs1162602317 CA352668603	130	V>D		No	ClinGen TOPMed
rs367621951 CA2387890	130	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs761632702 CA2387893	133	S>C		No	ClinGen ExAC TOPMed gnomAD
CA2387892 rs761632702	133	S>F		No	ClinGen ExAC TOPMed gnomAD
rs566139192 CA74011450	135	P>H		No	ClinGen TOPMed gnomAD
rs746152958 CA2387895	138	H>Y		No	ClinGen ExAC TOPMed gnomAD
CA74011469 rs201979858	139	C>*		No	ClinGen 1000Genomes
CA352669169 rs1292201451	144	Q>H		No	ClinGen gnomAD
rs995636397 CA74011471	145	F>L		No	ClinGen TOPMed gnomAD
rs554254556 CA2387897	147	R>*		No	ClinGen 1000Genomes ExAC gnomAD
rs554254556 CA2387896	147	R>G		No	ClinGen 1000Genomes ExAC gnomAD
rs1270532962 CA352669230	147	R>Q		No	ClinGen TOPMed gnomAD
rs1338452691 CA352669240	148	K>E		No	ClinGen gnomAD
rs1202802481 CA352669285	148	K>N		No	ClinGen gnomAD
CA352669372 rs1220021601	150	N>T		No	ClinGen TOPMed
COSM1753258 rs1033760412 CA74011501	153	S>C	urinary_tract [Cosmic]	No	ClinGen cosmic curated TOPMed
CA74011502 rs921369653	159	Q>R		No	ClinGen Ensembl
CA74011505 rs932796208	162	R>H		No	ClinGen gnomAD
rs1559827017 CA352669819	163	S>C		No	ClinGen Ensembl
rs1422549007 CA352669831	163	S>N		No	ClinGen gnomAD
CA2387899 rs780747982	167	Q>K		No	ClinGen ExAC gnomAD
rs752393082 CA2387900	168	H>Q		No	ClinGen ExAC gnomAD
rs1296781414 CA352670106	169	C>G		No	ClinGen TOPMed
COSM460782 rs201245336 CA2387902	173	V>I	cervix haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs1399500675 CA352670374	175	D>N		No	ClinGen gnomAD
rs1318844980 CA352670441	176	G>S		No	ClinGen gnomAD
CA2387905 rs780202533	177	V>M		No	ClinGen ExAC TOPMed gnomAD
CA352670557 rs1305429095	178	G>D		No	ClinGen gnomAD
CA2387907 rs768746772	179	V>M		No	ClinGen ExAC gnomAD
CA2387936 rs763886213	187	D>E		No	ClinGen ExAC TOPMed gnomAD
CA352672322 rs1336132245	187	D>G		No	ClinGen TOPMed gnomAD
CA2387935 rs760428061	187	D>N		No	ClinGen ExAC gnomAD
rs1264418280 CA352672400	189	P>S		No	ClinGen gnomAD
rs753506586 CA2387937	191	R>C		No	ClinGen ExAC gnomAD
CA2387938 rs546937892	191	R>H		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs753506586 CA74012510	191	R>S		No	ClinGen ExAC gnomAD
CA2387939 rs766749204	192	T>I		No	ClinGen ExAC gnomAD
rs962077158 CA74012522	194	E>D		No	ClinGen TOPMed
CA74012530 rs200216731	198	F>L		No	ClinGen Ensembl
CA352672894 rs1423230644	203	N>D		No	ClinGen gnomAD
rs112266750 CA2387943	203	N>S		No	ClinGen ExAC TOPMed gnomAD
rs529167013 CA74012555	211	R>G		No	ClinGen 1000Genomes
rs778037511 CA352673265	211	R>S		No	ClinGen ExAC TOPMed gnomAD
CA2387945 rs778037511	211	R>S		No	ClinGen ExAC TOPMed gnomAD
CA352673272 rs1370190130	212	R>C		No	ClinGen TOPMed gnomAD
rs867071514 CA74012559	212	R>H		No	ClinGen Ensembl
rs1391502628 CA352673405	216	R>K		No	ClinGen TOPMed
rs144088007 CA2387947	218	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA2387965 rs757464607	222	H>Q		No	ClinGen ExAC gnomAD
rs1486189292 CA352674505	237	I>M		No	ClinGen gnomAD
rs746926650 CA2387970	238	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA2387969 rs775632661	238	R>W		No	ClinGen ExAC gnomAD
rs768290698 CA2387971	241	E>K		No	ClinGen ExAC TOPMed
CA352674699 rs1338501907	246	R>Q		No	ClinGen Ensembl
rs776140482 CA2387972	247	V>I		No	ClinGen ExAC TOPMed gnomAD
CA2387973 rs376123571	250	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA2387975 rs772715889	251	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs769437830 CA2387974	251	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1436550025 CA352674941	253	N>S		No	ClinGen TOPMed gnomAD
CA352674976 rs767856740	254	E>D		No	ClinGen ExAC gnomAD
CA352675010 rs1355027825	255	V>A		No	ClinGen TOPMed gnomAD
rs1172186572 CA352674981	255	V>I		No	ClinGen TOPMed
CA2387994 rs762534832	259	K>Q		No	ClinGen ExAC gnomAD
CA2387995 rs772431690	261	R>C		No	ClinGen ExAC gnomAD
rs980773694 COSM3824095 CA74014661	261	R>H	breast [Cosmic]	No	ClinGen cosmic curated TOPMed
rs980773694 CA352676637	261	R>L		No	ClinGen TOPMed
rs761197257 CA2387997	266	A>S		No	ClinGen ExAC TOPMed gnomAD
CA352677129 rs1472921582	274	R>Q		No	ClinGen gnomAD
rs762017329 CA2388000	275	K>R		No	ClinGen ExAC gnomAD
CA2388002 rs750666445	278	T>M		No	ClinGen ExAC TOPMed gnomAD
rs866392304 CA74014688	283	D>N		No	ClinGen TOPMed
CA2388006 rs754796526	291	S>N		No	ClinGen ExAC gnomAD
CA352677847 rs1330422321	294	T>A		No	ClinGen gnomAD
rs1228012437 CA352678976	300	C>R		No	ClinGen gnomAD
CA2388024 rs751798787	310	C>Y		No	ClinGen ExAC gnomAD
rs370396255 CA2388037	317	K>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1252116594 CA352680221	320	H>Y		No	ClinGen TOPMed
rs753773992 CA2388049	329	D>N		No	ClinGen ExAC gnomAD
COSM1183598 CA352683143 rs1188915884	342	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed
CA2388050 rs756815478	342	R>H		No	ClinGen ExAC gnomAD
rs750091114 CA2388052	345	E>G		No	ClinGen ExAC gnomAD
COSM1172989 CA2388055 rs748510233	350	V>M	oesophagus [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed
rs1287785394 CA352683495	353	S>G		No	ClinGen TOPMed
rs200594843 CA2388058	356	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1388853437 CA352683623	357	Q>*		No	ClinGen TOPMed gnomAD
rs1227050558 CA352683687	358	A>V		No	ClinGen gnomAD
rs1576564543 CA352685919	376	N>S		No	ClinGen Ensembl
rs1395797554 CA352686376	386	Y>C		No	ClinGen gnomAD
rs1430538617 CA352686352	386	Y>H		No	ClinGen TOPMed
CA2388072 rs757902535	388	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA2388074 rs751218573	390	H>Q		No	ClinGen ExAC TOPMed gnomAD
CA2388076 COSM1045976 rs778218697	391	E>K	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC
CA352686833 rs771517976	396	R>S		No	ClinGen ExAC gnomAD
CA352686872 rs1211620874	398	M>T		No	ClinGen gnomAD
CA2388079 rs779542145	399	N>S		No	ClinGen ExAC
rs1237927374 CA352686944	400	N>S		No	ClinGen gnomAD
CA352687100 rs1559867992	406	D>N		No	ClinGen Ensembl
CA74016857 rs76267185	409	Y>D		No	ClinGen Ensembl
rs772190175 CA2388081	412	N>I		No	ClinGen ExAC TOPMed gnomAD
CA74016862 rs918121667	415	K>R		No	ClinGen TOPMed gnomAD
rs758425518 CA2388103	421	R>*		No	ClinGen ExAC TOPMed gnomAD
CA2388107 rs776808107	435	E>K		No	ClinGen ExAC gnomAD
rs769571023 CA2388109	437	G>R		No	ClinGen ExAC TOPMed gnomAD
rs773081132 CA2388110	438	P>S		No	ClinGen ExAC gnomAD
rs111941464 CA74017252	440	K>R		No	ClinGen Ensembl
CA74017559 rs112257171	447	Q>R		No	ClinGen Ensembl
CA352690275 rs373636239	460	K>R		No	ClinGen ESP TOPMed gnomAD
CA74017564 rs373636239	460	K>T		No	ClinGen ESP TOPMed gnomAD
rs1559875485 CA352691040	478	I>V		No	ClinGen Ensembl
rs1333235363 CA352691201	482	R>G		No	ClinGen gnomAD
CA2388147 rs749150125	482	R>Q		No	ClinGen ExAC gnomAD
CA352691310 rs1300024418	485	T>S		No	ClinGen gnomAD
rs1186572296 CA352691590	491	H>Q		No	ClinGen TOPMed
CA2388150 rs745744423	492	D>A		No	ClinGen ExAC TOPMed gnomAD
rs771716485 CA2388151	493	T>I		No	ClinGen ExAC gnomAD
rs771716485 CA352691640	493	T>N		No	ClinGen ExAC gnomAD

No associated diseases with O95376

3 regional properties for O95376

Type	Name	Position	InterPro Accession
domain	Pectinesterase, catalytic	207 - 504	IPR000070
domain	Pectinesterase inhibitor domain	4 - 167	IPR006501
active_site	Pectinesterase, Asp active site	351 - 360	IPR033131

Functions

		Description
EC Number	2.3.2.31	Aminoacyltransferases
Subcellular Localization	Nucleus Cytoplasm
PANTHER Family	PTHR11685	RBR FAMILY RING FINGER AND IBR DOMAIN-CONTAINING
PANTHER Subfamily	PTHR11685:SF210	E3 UBIQUITIN-PROTEIN LIGASE ARIH2
PANTHER Protein Class	ubiquitin-protein ligase protein modifying enzyme
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
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.
ubiquitin ligase complex	A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex.

4 GO annotations of molecular function

Name	Definition
ubiquitin conjugating enzyme binding	Binding to a ubiquitin conjugating enzyme, any of the E2 proteins.
ubiquitin protein ligase activity	Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S -> X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues.
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.
zinc ion binding	Binding to a zinc ion (Zn).

9 GO annotations of biological process

Name	Definition
developmental cell growth	The growth of a cell, where growth contributes to the progression of the cell over time from one condition to another.
hematopoietic stem cell proliferation	The expansion of a hematopoietic stem cell population by cell division. A hematopoietic stem cell is a stem cell from which all cells of the lymphoid and myeloid lineages develop.
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	Any process that activates or increases the frequency, rate or extent of 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.
positive regulation of protein targeting to mitochondrion	Any process that activates or increases the frequency, rate or extent of protein targeting to mitochondrion.
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 K63-linked ubiquitination	A protein ubiquitination process in which a polymer of ubiquitin, formed by linkages between lysine residues at position 63 of the ubiquitin monomers, is added to a protein. K63-linked ubiquitination does not target the substrate protein for degradation, but is involved in several pathways, notably as a signal to promote error-free DNA postreplication repair.
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.
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.

13 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
A2VEA3	ARIH1	E3 ubiquitin-protein ligase ARIH1	Bos taurus (Bovine)	SS
O76924	ari-2	Potential E3 ubiquitin-protein ligase ariadne-2	Drosophila melanogaster (Fruit fly)	SS
Q94981	ari-1	E3 ubiquitin-protein ligase ariadne-1	Drosophila melanogaster (Fruit fly)	SS
Q9NWF9	RNF216	E3 ubiquitin-protein ligase RNF216	Homo sapiens (Human)	PR
O60260	PRKN	E3 ubiquitin-protein ligase parkin	Homo sapiens (Human)	EV
Q9Y4X5	ARIH1	E3 ubiquitin-protein ligase ARIH1	Homo sapiens (Human)	EV
Q9Z1K6	Arih2	E3 ubiquitin-protein ligase ARIH2	Mus musculus (Mouse)	SS
Q9Z1K5	Arih1	E3 ubiquitin-protein ligase ARIH1	Mus musculus (Mouse)	SS
Q22431	ari-2	Potential E3 ubiquitin-protein ligase ariadne-2	Caenorhabditis elegans	SS
O01965	ari-1.1	E3 ubiquitin-protein ligase ari-1.1	Caenorhabditis elegans	SS
B1H1E4	arih1	E3 ubiquitin-protein ligase arih1	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS
Q6PFJ9	arih1	E3 ubiquitin-protein ligase arih1	Danio rerio (Zebrafish) (Brachydanio rerio)	SS
Q6NW85	arih1l	E3 ubiquitin-protein ligase arih1l	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MSVDMNSQGS	DSNEEDYDPN	CEEEEEEEED	DPGDIEDYYV	GVASDVEQQG	ADAFDPEEYQ
70	80	90	100	110	120
FTCLTYKESE	GALNEHMTSL	ASVLKVSHSV	AKLILVNFHW	QVSEILDRYK	SNSAQLLVEA
130	140	150	160	170	180
RVQPNPSKHV	PTSHPPHHCA	VCMQFVRKEN	LLSLACQHQF	CRSCWEQHCS	VLVKDGVGVG
190	200	210	220	230	240
VSCMAQDCPL	RTPEDFVFPL	LPNEELREKY	RRYLFRDYVE	SHYQLQLCPG	ADCPMVIRVQ
250	260	270	280	290	300
EPRARRVQCN	RCNEVFCFKC	RQMYHAPTDC	ATIRKWLTKC	ADDSETANYI	SAHTKDCPKC
310	320	330	340	350	360
NICIEKNGGC	NHMQCSKCKH	DFCWMCLGDW	KTHGSEYYEC	SRYKENPDIV	NQSQQAQARE
370	380	390	400	410	420
ALKKYLFYFE	RWENHNKSLQ	LEAQTYQRIH	EKIQERVMNN	LGTWIDWQYL	QNAAKLLAKC
430	440	450	460	470	480
RYTLQYTYPY	AYYMESGPRK	KLFEYQQAQL	EAEIENLSWK	VERADSYDRG	DLENQMHIAE
490
QRRRTLLKDF	HDT