Reviewed, UniProtKB/Swiss-Prot Q7Z6Z7 (HUWE1_HUMAN)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase HUWE1
    EC=6.3.2.-
Alternative name(s):
    HECT, UBA and WWE domain-containing protein 1
    Upstream regulatory element-binding protein 1
      Short name=URE-binding protein 1
      Short name=URE-B1
    Mcl-1 ubiquitin ligase E3
      Short name=Mule
    ARF-binding protein 1
      Short name=ARF-BP1
    Large structure of UREB1
      Short name=LASU1
    Homologous to E6AP carboxyl terminus homologous protein 9
      Short name=HectH9

Gene names

Name:	HUWE1
Synonyms:	KIAA0312, KIAA1578, UREB1
ORF Names:	HSPC272

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	4374 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Also ubiquitinates the p53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4. Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation. Ref.1 Ref.2 Ref.3 Ref.14 Ref.17 Ref.23
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with isoform p14ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity. Interacts with MYCN and CDC6. Ref.1 Ref.17 Ref.23
Subcellular location	Cytoplasm. Nucleus. Note: Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells By similarity. Predominantly cytosolic or perinuclear in some colorectal carcinoma cells.
Tissue specificity	Weakly expressed in heart, brain and placenta but not in other tissues. Expressed in a number of cell lines, predominantly in those from colorectal carcinomas. Ref.14
Domain	The HECT domain mediates inhibition of the transcriptional activity of p53.
Post-translational modification	Phosphorylated on tyrosine; phosphorylation is probably required for its ability to inhibit TP53 transactivation By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.13 Ref.15 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24
Involvement in disease	Defects in HUWE1 are the cause of mental retardation syndromic X-linked Turner type (MRXST) [MIM:300706]; also known as mental retardation and macrocephaly syndrome. MRXST shows clinical variability. Associated phenotypes include macrocephaly and variable contractures. A chromosomal microduplication involving HUWE1 and HSD17B10 is the cause of mental retardation X-linked type 17 (MRX17) [MIM:300705]; also known as mental retardation X-linked type 31 (MRX31). Mental retardation is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. In contrast to syndromic or specific X-linked mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation. Ref.26
Sequence similarities	Belongs to the TOM1/PTR1 family. Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. Contains 1 UBA domain. Contains 1 UIM (ubiquitin-interacting motif) repeat. Contains 1 WWE domain.
Sequence caution	The sequence AAF28950.1 differs from that shown. Reason: Frameshift at position 4356. The sequence BAB13404.1 differs from that shown. Reason: Miscellaneous discrepancy. Chimeric cDNA, contains the C-terminal part of ATP5I. The sequence BAC06833.1 differs from that shown. Reason: Frameshift at positions 982 and 1055.

Ontologies

Keywords
Biological process	Differentiation Ubl conjugation pathway
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Disease mutation Mental retardation
Ligand	DNA-binding
Molecular function	Ligase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW histone ubiquitination Ref.3 Inferred from direct assay. Source: UniProtKB modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW protein polyubiquitination Ref.2 Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	DNA binding Inferred from sequence or structural similarity. Source: UniProtKB protein binding Ref.1 Inferred from physical interaction. Source: IntAct ubiquitin-protein ligase activity Ref.2 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDKN2A	Q8N726	2	EBI-625934,EBI-625922
TP53	P04637	2	EBI-625934,EBI-366083

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z6Z7-1)

Also known as: LASU1; Large structure of UREB1;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q7Z6Z7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     3016-3031: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q7Z6Z7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     982-990: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 4374

4374

E3 ubiquitin-protein ligase HUWE1

PRO_0000120340

Regions

Domain

1316 – 1355

40

UBA

Repeat

1370 – 1389

20

UIM

Domain

1603 – 1680

78

WWE

Domain

4038 – 4374

337

HECT

Compositional bias

2295 – 2469

175

Glu-rich

Compositional bias

2427 – 2490

64

Asp-rich

Compositional bias

3483 – 3550

68

Thr-rich

Sites

Active site

4341

1

Glycyl thioester intermediate

Amino acid modifications

Modified residue

509

1

N6-acetyllysine Ref.25

Modified residue

1084

1

Phosphoserine Ref.21

Modified residue

1368

1

Phosphoserine Ref.24

Modified residue

1395

1

Phosphoserine Ref.13 Ref.16 Ref.24

Modified residue

1840

1

N6-acetyllysine Ref.25

Modified residue

1907

1

Phosphoserine Ref.13 Ref.15 Ref.16 Ref.19 Ref.20 Ref.22 Ref.24

Modified residue

2248

1

N6-acetyllysine Ref.25

Modified residue

2362

1

Phosphoserine Ref.13 Ref.15 Ref.16 Ref.22 Ref.24

Modified residue

2365

1

Phosphoserine Ref.24

Modified residue

2377

1

Phosphoserine Ref.18

Modified residue

2526

1

Phosphoserine Ref.21

Modified residue

2887

1

Phosphoserine Ref.16 Ref.24

Modified residue

2918

1

Phosphoserine Ref.16

Modified residue

3662

1

Phosphoserine Ref.24

Modified residue

3757

1

Phosphoserine By similarity

Modified residue

3797

1

Phosphoserine Ref.18

Modified residue

3808

1

Phosphoserine Ref.15

Modified residue

3816

1

Phosphoserine Ref.15 Ref.18

Modified residue

3822

1

Phosphothreonine Ref.18

Modified residue

3919

1

Phosphoserine Ref.15 Ref.24

Modified residue

3924

1

Phosphothreonine Ref.15 Ref.24

Modified residue

3927

1

Phosphothreonine Ref.15 Ref.24

Modified residue

4271

1

Phosphotyrosine By similarity

Natural variations

Alternative sequence

982 – 990

9

Missing in isoform 3.

VSP_015272

Alternative sequence

3016 – 3031

16

Missing in isoform 2.

VSP_011146

Natural variant

2981

1

R → H in MRXS-Turner. Ref.26

VAR_045670

Natural variant

4013

1

R → W in MRXS-Turner. Ref.26

VAR_045671

Natural variant

4187

1

R → C in MRXS-Turner. Ref.26

VAR_045672

Experimental info

Mutagenesis

4268

1

Y → S: Loss of activity. Ref.14

Mutagenesis

4341

1

C → A or D: Loss of activity. Ref.1 Ref.2 Ref.14 Ref.23

Sequence conflict

1111

1

K → N Ref.5

Sequence conflict

1124

1

P → L Ref.1

Sequence conflict

1124

1

P → L Ref.5

Sequence conflict

1190

1

D → H Ref.5

Sequence conflict

1962

1

Missing Ref.6

Sequence conflict

2310

1

Q → H Ref.6

Sequence conflict

2451 – 2453

3

GEE → ARG Ref.8

Sequence conflict

2525

1

H → Y Ref.5

Sequence conflict

2525

1

H → Y Ref.8

Sequence conflict

4022

1

R → L in AAH02602. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

4374

Helix Strand Turn

Details...

Helix

4006 – 4009

4

Beta strand

4016 – 4021

6

Helix

4023 – 4025

3

Helix

4026 – 4034

9

Helix

4041 – 4043

3

Beta strand

4044 – 4050

7

Helix

4062 – 4072

11

Turn

4076 – 4078

3

Beta strand

4081 – 4083

3

Beta strand

4091 – 4093

3

Helix

4095 – 4099

5

Helix

4103 – 4109

7

Helix

4113 – 4119

7

Helix

4130 – 4136

7

Helix

4143 – 4146

4

Turn

4147 – 4149

3

Helix

4151 – 4154

4

Helix

4158 – 4161

4

Turn

4165 – 4167

3

Beta strand

4173 – 4179

7

Beta strand

4184 – 4190

7

Turn

4200 – 4202

3

Helix

4203 – 4215

13

Helix

4220 – 4227

8

Turn

4231 – 4233

3

Helix

4236 – 4239

4

Helix

4244 – 4251

8

Helix

4259 – 4263

5

Beta strand

4266 – 4271

6

Helix

4276 – 4286

11

Helix

4290 – 4300

11

Beta strand

4323 – 4326

4

Beta strand

4337 – 4339

3

Helix

4340 – 4342

3

Beta strand

4344 – 4346

3

Helix

4353 – 4363

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (LASU1) (Large structure of UREB1) [UniParc]. Last modified August 30, 2005. Version 3. Checksum: FA9D3A7712F6393B	FASTA	4,374	481,891
	10 20 30 40 50 60 MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE LYHWVDLLDR 70 80 90 100 110 120 FDGILADAGQ TVENMSWMLV CDRPEREQLK MLLLAVLNFT ALLIEYSFSR HLYSSIEHLT 130 140 150 160 170 180 TLLASSDMQV VLAVLNLLYV FSKRSNYITR LGSDKRTPLL TRLQHLAESW GGKENGFGLA 190 200 210 220 230 240 ECCRDLHMMK YPPSATTLHF EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM 250 260 270 280 290 300 ESLTKMYSIP KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI 310 320 330 340 350 360 LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT GTASYHGFLP 370 380 390 400 410 420 VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG EALVSCGMME ALLKVIKFLG 430 440 450 460 470 480 DEQDQITFVT RAVRVVDLIT NLDMAAFQSH SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ 490 500 510 520 530 540 RPNTTQEGEE METDMDGVQC IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL 550 560 570 580 590 600 KHIISNAEYY GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV 610 620 630 640 650 660 LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD PLGDTASNLG 670 680 690 700 710 720 SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ KPSIQKADGT ATAPPPRSNH 730 740 750 760 770 780 AAEEASSEDE EEEEVQAMQS FNSTQQNETE PNQQVVGTEE RIPIPLMDYI LNVMKFVESI 790 800 810 820 830 840 LSNNTTDDHC QEFVNQKGLL PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV 850 860 870 880 890 900 LQEGLLQLDS ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH 910 920 930 940 950 960 AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV LLSLCTPNSL 970 980 990 1000 1010 1020 PSGCEFGQAD MQKLVPKDEK AGTTQGGKRS DGEQDGAAGS MDASTQGLLE GIGLDGDTLA 1030 1040 1050 1060 1070 1080 PMETDEPTAS DSKGKSKITP AMAARIKQIK PLLSASSRLG RALAELFGLL VKLCVGSPVR 1090 1100 1110 1120 1130 1140 QRRSHHAAST TTAPTPAARS TASALTKLLT KGLSWQPPPY TPTPRFRLTF FICSVGFTSP 1150 1160 1170 1180 1190 1200 MLFDERKYPY HLMLQKFLCS GGHNALFETF NWALSMGGKV PVSEGLEHSD LPDGTGEFLD 1210 1220 1230 1240 1250 1260 AWLMLVEKMV NPTTVLESPH SLPAKLPGGV QNFPQFSALR FLVVTQKAAF TCIKNLWNRK 1270 1280 1290 1300 1310 1320 PLKVYGGRMA ESMLAILCHI LRGEPVIRER LSKEKEGSRG EEDTGQEEGG SRREPQVNQQ 1330 1340 1350 1360 1370 1380 QLQQLMDMGF TREHAMEALL NTSTMEQATE YLLTHPPPIM GGVVRDLSMS EEDQMMRAIA 1390 1400 1410 1420 1430 1440 MSLGQDIPMD QRAESPEEVA CRKEEEERKA REKQEEEEAK CLEKFQDADP LEQDELHTFT 1450 1460 1470 1480 1490 1500 DTMLPGCFHL LDELPDTVYR VCDLIMTAIK RNGADYRDMI LKQVVNQVWE AADVLIKAAL 1510 1520 1530 1540 1550 1560 PLTTSDTKTV SEWISQMATL PQASNLATRI LLLTLLFEEL KLPCAWVVES SGILNVLIKL 1570 1580 1590 1600 1610 1620 LEVVQPCLQA AKEQKEVQTP KWITPVLLLI DFYEKTAISS KRRAQMTKYL QSNSNNWRWF 1630 1640 1650 1660 1670 1680 DDRSGRWCSY SASNNSTIDS AWKSGETSVR FTAGRRRYTV QFTTMVQVNE ETGNRRPVML 1690 1700 1710 1720 1730 1740 TLLRVPRLNK NSKNSNGQEL EKTLEESKEM DIKRKENKGN DTPLALESTN TEKETSLEET 1750 1760 1770 1780 1790 1800 KIGEILIQGL TEDMVTVLIR ACVSMLGVPV DPDTLHATLR LCLRLTRDHK YAMMFAELKS 1810 1820 1830 1840 1850 1860 TRMILNLTQS SGFNGFTPLV TLLLRHIIED PCTLRHTMEK VVRSAATSGA GSTTSGVVSG 1870 1880 1890 1900 1910 1920 SLGSREINYI LRVLGPAACR NPDIFTEVAN CCIRIALPAP RGSGTASDDE FENLRIKGPN 1930 1940 1950 1960 1970 1980 AVQLVKTTPL KPSPLPVIPD TIKEVIYDML NALAAYHAPE EADKSDPKPG VMTQEVGQLL 1990 2000 2010 2020 2030 2040 QDMGDDVYQQ YRSLTRQSSD FDTQSGFSIN SQVFAADGAS TETSASGTSQ GEASTPEESR 2050 2060 2070 2080 2090 2100 DGKKDKEGDR ASEEGKQKGK GSKPLMPTST ILRLLAELVR SYVGIATLIA NYSYTVGQSE 2110 2120 2130 2140 2150 2160 LIKEDCSVLA FVLDHLLPHT QNAEDKDTPA LARLFLASLA AAGSGTDAQV ALVNEVKAAL 2170 2180 2190 2200 2210 2220 GRALAMAEST EKHARLQAVM CIISTIMESC PSTSSFYSSA TAKTQHNGMN NIIRLFLKKG 2230 2240 2250 2260 2270 2280 LVNDLARVPH SLDLSSPNMA NTVNAALKPL ETLSRIVNQP SSLFGSKSAS SKNKSEQDAQ 2290 2300 2310 2320 2330 2340 GASQDSSSNQ QDPGEPGEAE VQEEDHDVTQ TEVADGDIMD GEAETDSVVI AGQPEVLSSQ 2350 2360 2370 2380 2390 2400 EMQVENELED LIDELLERDG GSGNSTIIVS RSGEDESQED VLMDEAPSNL SQASTLQANR 2410 2420 2430 2440 2450 2460 EDSMNILDPE DEEEHTQEED SSGSNEDEDD SQDEEEEEEE DEEDDQEDDE GEEGDEDDDD 2470 2480 2490 2500 2510 2520 DGSEMELDED YPDMNASPLV RFERFDREDD LIIEFDNMFS SATDIPPSPG NIPTTHPLMV 2530 2540 2550 2560 2570 2580 RHADHSSLTL GSGSSTTRLT QGIGRSQRTL RQLTANTGHT IHVHYPGNRQ PNPPLILQRL 2590 2600 2610 2620 2630 2640 LGPSAAADIL QLSSSLPLQS RGRARLLVGN DDVHIIARSD DELLDDFFHD QSTATSQAGT 2650 2660 2670 2680 2690 2700 LSSIPTALTR WTEECKVLDA ESMHDCVSVV KVSIVNHLEF LRDEELEERR EKRRKQLAEE 2710 2720 2730 2740 2750 2760 ETKITDKGKE DKENRDQSAQ CTASKSNDST EQNLSDGTPM PDSYPTTPSS TDAATSESKE 2770 2780 2790 2800 2810 2820 TLGTLQSSQQ QPTLPTPPAL GEVPQELQSP AGEGGSSTQL LMPVEPEELG PTRPSGEAET 2830 2840 2850 2860 2870 2880 TQMELSPAPT ITSLSPERAE DSDALTAVSS QLEGSPMDTS SLASCTLEEA VGDTSAAGSS 2890 2900 2910 2920 2930 2940 EQPRAGSSTP GDAPPAVAEV QGRSDGSGES AQPPEDSSPP ASSESSSTRD SAVAISGADS 2950 2960 2970 2980 2990 3000 RGILEEPLPS TSSEEEDPLA GISLPEGVDP SFLAALPDDI RREVLQNQLG IRPPTRTAPS 3010 3020 3030 3040 3050 3060 TNSSAPAVVG NPGVTEVSPE FLAALPPAIQ EEVLAQQRAE QQRRELAQNA SSDTPMDPVT 3070 3080 3090 3100 3110 3120 FIQTLPSDLR RSVLEDMEDS VLAVMPPDIA AEAQALRREQ EARQRQLMHE RLFGHSSTSA 3130 3140 3150 3160 3170 3180 LSAILRSPAF TSRLSGNRGV QYTRLAVQRG GTFQMGGSSS HNRPSGSNVD TLLRLRGRLL 3190 3200 3210 3220 3230 3240 LDHEALSCLL VLLFVDEPKL NTSRLHRVLR NLCYHAQTRH WVIRSLLSIL QRSSESELCI 3250 3260 3270 3280 3290 3300 ETPKLTTSEE KGKKSSKSCG SSSHENRPLD LLHKMESKSS NQLSWLSVSM DAALGCRTNI 3310 3320 3330 3340 3350 3360 FQIQRSGGRK HTEKHASGGS TVHIHPQAAP VVCRHVLDTL IQLAKVFPSH FTQQRTKETN 3370 3380 3390 3400 3410 3420 CESDRERGNK ACSPCSSQSS SSGICTDFWD LLVKLDNMNV SRKGKNSVKS VPVSAGGEGE 3430 3440 3450 3460 3470 3480 TSPYSLEASP LGQLMNMLSH PVIRRSSLLT EKLLRLLSLI SIALPENKVS EAQANSGSGA 3490 3500 3510 3520 3530 3540 SSTTTATSTT STTTTTAAST TPTPPTAPTP VTSAPALVAA TAISTIVVAA STTVTTPTTA 3550 3560 3570 3580 3590 3600 TTTVSISPTT KGSKSPAKVS DGGSSSTDFK MVSSGLTENQ LQLSVEVLTS HSCSEEGLED 3610 3620 3630 3640 3650 3660 AANVLLQLSR GDSGTRDTVL KLLLNGARHL GYTLCKQIGT LLAELREYNL EQQRRAQCET 3670 3680 3690 3700 3710 3720 LSPDGLPEEQ PQTTKLKGKM QSRFDMAENV VIVASQKRPL GGRELQLPSM SMLTSKTSTQ 3730 3740 3750 3760 3770 3780 KFFLRVLQVI IQLRDDTRRA NKKAKQTGRL GSSGLGSASS IQAAVRQLEA EADAIIQMVR 3790 3800 3810 3820 3830 3840 EGQRARRQQQ AATSESSQSE ASVRREESPM DVDQPSPSAQ DTQSIASDGT PQGEKEKEER 3850 3860 3870 3880 3890 3900 PPELPLLSEQ LSLDELWDML GECLKELEES HDQHAVLVLQ PAVEAFFLVH ATERESKPPV 3910 3920 3930 3940 3950 3960 RDTRESQLAH IKDEPPPLSP APLTPATPSS LDPFFSREPS SMHISSSLPP DTQKFLRFAE 3970 3980 3990 4000 4010 4020 THRTVLNQIL RQSTTHLADG PFAVLVDYIR VLDFDVKRKY FRQELERLDE GLRKEDMAVH 4030 4040 4050 4060 4070 4080 VRRDHVFEDS YRELHRKSPE EMKNRLYIVF EGEEGQDAGG LLREWYMIIS REMFNPMYAL 4090 4100 4110 4120 4130 4140 FRTSPGDRVT YTINPSSHCN PNHLSYFKFV GRIVAKAVYD NRLLECYFTR SFYKHILGKS 4150 4160 4170 4180 4190 4200 VRYTDMESED YHFYQGLVYL LENDVSTLGY DLTFSTEVQE FGVCEVRDLK PNGANILVTE 4210 4220 4230 4240 4250 4260 ENKKEYVHLV CQMRMTGAIR KQLAAFLEGF YEIIPKRLIS IFTEQELELL ISGLPTIDID 4270 4280 4290 4300 4310 4320 DLKSNTEYHK YQSNSIQIQW FWRALRSFDQ ADRAKFLQFV TGTSKVPLQG FAALEGMNGI 4330 4340 4350 4360 4370 QKFQIHRDDR STDRLPSAHT CFNQLDLPAY ESFEKLRHML LLAIQECSEG FGLA
	Isoform 2. Checksum: D30775B19F710F6F	FASTA	4,358	480,198
	10 20 30 40 50 60 MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE LYHWVDLLDR 70 80 90 100 110 120 FDGILADAGQ TVENMSWMLV CDRPEREQLK MLLLAVLNFT ALLIEYSFSR HLYSSIEHLT 130 140 150 160 170 180 TLLASSDMQV VLAVLNLLYV FSKRSNYITR LGSDKRTPLL TRLQHLAESW GGKENGFGLA 190 200 210 220 230 240 ECCRDLHMMK YPPSATTLHF EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM 250 260 270 280 290 300 ESLTKMYSIP KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI 310 320 330 340 350 360 LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT GTASYHGFLP 370 380 390 400 410 420 VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG EALVSCGMME ALLKVIKFLG 430 440 450 460 470 480 DEQDQITFVT RAVRVVDLIT NLDMAAFQSH SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ 490 500 510 520 530 540 RPNTTQEGEE METDMDGVQC IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL 550 560 570 580 590 600 KHIISNAEYY GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV 610 620 630 640 650 660 LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD PLGDTASNLG 670 680 690 700 710 720 SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ KPSIQKADGT ATAPPPRSNH 730 740 750 760 770 780 AAEEASSEDE EEEEVQAMQS FNSTQQNETE PNQQVVGTEE RIPIPLMDYI LNVMKFVESI 790 800 810 820 830 840 LSNNTTDDHC QEFVNQKGLL PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV 850 860 870 880 890 900 LQEGLLQLDS ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH 910 920 930 940 950 960 AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV LLSLCTPNSL 970 980 990 1000 1010 1020 PSGCEFGQAD MQKLVPKDEK AGTTQGGKRS DGEQDGAAGS MDASTQGLLE GIGLDGDTLA 1030 1040 1050 1060 1070 1080 PMETDEPTAS DSKGKSKITP AMAARIKQIK PLLSASSRLG RALAELFGLL VKLCVGSPVR 1090 1100 1110 1120 1130 1140 QRRSHHAAST TTAPTPAARS TASALTKLLT KGLSWQPPPY TPTPRFRLTF FICSVGFTSP 1150 1160 1170 1180 1190 1200 MLFDERKYPY HLMLQKFLCS GGHNALFETF NWALSMGGKV PVSEGLEHSD LPDGTGEFLD 1210 1220 1230 1240 1250 1260 AWLMLVEKMV NPTTVLESPH SLPAKLPGGV QNFPQFSALR FLVVTQKAAF TCIKNLWNRK 1270 1280 1290 1300 1310 1320 PLKVYGGRMA ESMLAILCHI LRGEPVIRER LSKEKEGSRG EEDTGQEEGG SRREPQVNQQ 1330 1340 1350 1360 1370 1380 QLQQLMDMGF TREHAMEALL NTSTMEQATE YLLTHPPPIM GGVVRDLSMS EEDQMMRAIA 1390 1400 1410 1420 1430 1440 MSLGQDIPMD QRAESPEEVA CRKEEEERKA REKQEEEEAK CLEKFQDADP LEQDELHTFT 1450 1460 1470 1480 1490 1500 DTMLPGCFHL LDELPDTVYR VCDLIMTAIK RNGADYRDMI LKQVVNQVWE AADVLIKAAL 1510 1520 1530 1540 1550 1560 PLTTSDTKTV SEWISQMATL PQASNLATRI LLLTLLFEEL KLPCAWVVES SGILNVLIKL 1570 1580 1590 1600 1610 1620 LEVVQPCLQA AKEQKEVQTP KWITPVLLLI DFYEKTAISS KRRAQMTKYL QSNSNNWRWF 1630 1640 1650 1660 1670 1680 DDRSGRWCSY SASNNSTIDS AWKSGETSVR FTAGRRRYTV QFTTMVQVNE ETGNRRPVML 1690 1700 1710 1720 1730 1740 TLLRVPRLNK NSKNSNGQEL EKTLEESKEM DIKRKENKGN DTPLALESTN TEKETSLEET 1750 1760 1770 1780 1790 1800 KIGEILIQGL TEDMVTVLIR ACVSMLGVPV DPDTLHATLR LCLRLTRDHK YAMMFAELKS 1810 1820 1830 1840 1850 1860 TRMILNLTQS SGFNGFTPLV TLLLRHIIED PCTLRHTMEK VVRSAATSGA GSTTSGVVSG 1870 1880 1890 1900 1910 1920 SLGSREINYI LRVLGPAACR NPDIFTEVAN CCIRIALPAP RGSGTASDDE FENLRIKGPN 1930 1940 1950 1960 1970 1980 AVQLVKTTPL KPSPLPVIPD TIKEVIYDML NALAAYHAPE EADKSDPKPG VMTQEVGQLL 1990 2000 2010 2020 2030 2040 QDMGDDVYQQ YRSLTRQSSD FDTQSGFSIN SQVFAADGAS TETSASGTSQ GEASTPEESR 2050 2060 2070 2080 2090 2100 DGKKDKEGDR ASEEGKQKGK GSKPLMPTST ILRLLAELVR SYVGIATLIA NYSYTVGQSE 2110 2120 2130 2140 2150 2160 LIKEDCSVLA FVLDHLLPHT QNAEDKDTPA LARLFLASLA AAGSGTDAQV ALVNEVKAAL 2170 2180 2190 2200 2210 2220 GRALAMAEST EKHARLQAVM CIISTIMESC PSTSSFYSSA TAKTQHNGMN NIIRLFLKKG 2230 2240 2250 2260 2270 2280 LVNDLARVPH SLDLSSPNMA NTVNAALKPL ETLSRIVNQP SSLFGSKSAS SKNKSEQDAQ 2290 2300 2310 2320 2330 2340 GASQDSSSNQ QDPGEPGEAE VQEEDHDVTQ TEVADGDIMD GEAETDSVVI AGQPEVLSSQ 2350 2360 2370 2380 2390 2400 EMQVENELED LIDELLERDG GSGNSTIIVS RSGEDESQED VLMDEAPSNL SQASTLQANR 2410 2420 2430 2440 2450 2460 EDSMNILDPE DEEEHTQEED SSGSNEDEDD SQDEEEEEEE DEEDDQEDDE GEEGDEDDDD 2470 2480 2490 2500 2510 2520 DGSEMELDED YPDMNASPLV RFERFDREDD LIIEFDNMFS SATDIPPSPG NIPTTHPLMV 2530 2540 2550 2560 2570 2580 RHADHSSLTL GSGSSTTRLT QGIGRSQRTL RQLTANTGHT IHVHYPGNRQ PNPPLILQRL 2590 2600 2610 2620 2630 2640 LGPSAAADIL QLSSSLPLQS RGRARLLVGN DDVHIIARSD DELLDDFFHD QSTATSQAGT 2650 2660 2670 2680 2690 2700 LSSIPTALTR WTEECKVLDA ESMHDCVSVV KVSIVNHLEF LRDEELEERR EKRRKQLAEE 2710 2720 2730 2740 2750 2760 ETKITDKGKE DKENRDQSAQ CTASKSNDST EQNLSDGTPM PDSYPTTPSS TDAATSESKE 2770 2780 2790 2800 2810 2820 TLGTLQSSQQ QPTLPTPPAL GEVPQELQSP AGEGGSSTQL LMPVEPEELG PTRPSGEAET 2830 2840 2850 2860 2870 2880 TQMELSPAPT ITSLSPERAE DSDALTAVSS QLEGSPMDTS SLASCTLEEA VGDTSAAGSS 2890 2900 2910 2920 2930 2940 EQPRAGSSTP GDAPPAVAEV QGRSDGSGES AQPPEDSSPP ASSESSSTRD SAVAISGADS 2950 2960 2970 2980 2990 3000 RGILEEPLPS TSSEEEDPLA GISLPEGVDP SFLAALPDDI RREVLQNQLG IRPPTRTAPS 3010 3020 3030 3040 3050 3060 TNSSAPAVVG NPGVTEVLAQ QRAEQQRREL AQNASSDTPM DPVTFIQTLP SDLRRSVLED 3070 3080 3090 3100 3110 3120 MEDSVLAVMP PDIAAEAQAL RREQEARQRQ LMHERLFGHS STSALSAILR SPAFTSRLSG 3130 3140 3150 3160 3170 3180 NRGVQYTRLA VQRGGTFQMG GSSSHNRPSG SNVDTLLRLR GRLLLDHEAL SCLLVLLFVD 3190 3200 3210 3220 3230 3240 EPKLNTSRLH RVLRNLCYHA QTRHWVIRSL LSILQRSSES ELCIETPKLT TSEEKGKKSS 3250 3260 3270 3280 3290 3300 KSCGSSSHEN RPLDLLHKME SKSSNQLSWL SVSMDAALGC RTNIFQIQRS GGRKHTEKHA 3310 3320 3330 3340 3350 3360 SGGSTVHIHP QAAPVVCRHV LDTLIQLAKV FPSHFTQQRT KETNCESDRE RGNKACSPCS 3370 3380 3390 3400 3410 3420 SQSSSSGICT DFWDLLVKLD NMNVSRKGKN SVKSVPVSAG GEGETSPYSL EASPLGQLMN 3430 3440 3450 3460 3470 3480 MLSHPVIRRS SLLTEKLLRL LSLISIALPE NKVSEAQANS GSGASSTTTA TSTTSTTTTT 3490 3500 3510 3520 3530 3540 AASTTPTPPT APTPVTSAPA LVAATAISTI VVAASTTVTT PTTATTTVSI SPTTKGSKSP 3550 3560 3570 3580 3590 3600 AKVSDGGSSS TDFKMVSSGL TENQLQLSVE VLTSHSCSEE GLEDAANVLL QLSRGDSGTR 3610 3620 3630 3640 3650 3660 DTVLKLLLNG ARHLGYTLCK QIGTLLAELR EYNLEQQRRA QCETLSPDGL PEEQPQTTKL 3670 3680 3690 3700 3710 3720 KGKMQSRFDM AENVVIVASQ KRPLGGRELQ LPSMSMLTSK TSTQKFFLRV LQVIIQLRDD 3730 3740 3750 3760 3770 3780 TRRANKKAKQ TGRLGSSGLG SASSIQAAVR QLEAEADAII QMVREGQRAR RQQQAATSES 3790 3800 3810 3820 3830 3840 SQSEASVRRE ESPMDVDQPS PSAQDTQSIA SDGTPQGEKE KEERPPELPL LSEQLSLDEL 3850 3860 3870 3880 3890 3900 WDMLGECLKE LEESHDQHAV LVLQPAVEAF FLVHATERES KPPVRDTRES QLAHIKDEPP 3910 3920 3930 3940 3950 3960 PLSPAPLTPA TPSSLDPFFS REPSSMHISS SLPPDTQKFL RFAETHRTVL NQILRQSTTH 3970 3980 3990 4000 4010 4020 LADGPFAVLV DYIRVLDFDV KRKYFRQELE RLDEGLRKED MAVHVRRDHV FEDSYRELHR 4030 4040 4050 4060 4070 4080 KSPEEMKNRL YIVFEGEEGQ DAGGLLREWY MIISREMFNP MYALFRTSPG DRVTYTINPS 4090 4100 4110 4120 4130 4140 SHCNPNHLSY FKFVGRIVAK AVYDNRLLEC YFTRSFYKHI LGKSVRYTDM ESEDYHFYQG 4150 4160 4170 4180 4190 4200 LVYLLENDVS TLGYDLTFST EVQEFGVCEV RDLKPNGANI LVTEENKKEY VHLVCQMRMT 4210 4220 4230 4240 4250 4260 GAIRKQLAAF LEGFYEIIPK RLISIFTEQE LELLISGLPT IDIDDLKSNT EYHKYQSNSI 4270 4280 4290 4300 4310 4320 QIQWFWRALR SFDQADRAKF LQFVTGTSKV PLQGFAALEG MNGIQKFQIH RDDRSTDRLP 4330 4340 4350 SAHTCFNQLD LPAYESFEKL RHMLLLAIQE CSEGFGLA
	Isoform 3. Checksum: E8A8FFC3C7EB9B24	FASTA	4,365	481,018
	10 20 30 40 50 60 MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE LYHWVDLLDR 70 80 90 100 110 120 FDGILADAGQ TVENMSWMLV CDRPEREQLK MLLLAVLNFT ALLIEYSFSR HLYSSIEHLT 130 140 150 160 170 180 TLLASSDMQV VLAVLNLLYV FSKRSNYITR LGSDKRTPLL TRLQHLAESW GGKENGFGLA 190 200 210 220 230 240 ECCRDLHMMK YPPSATTLHF EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM 250 260 270 280 290 300 ESLTKMYSIP KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI 310 320 330 340 350 360 LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT GTASYHGFLP 370 380 390 400 410 420 VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG EALVSCGMME ALLKVIKFLG 430 440 450 460 470 480 DEQDQITFVT RAVRVVDLIT NLDMAAFQSH SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ 490 500 510 520 530 540 RPNTTQEGEE METDMDGVQC IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL 550 560 570 580 590 600 KHIISNAEYY GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV 610 620 630 640 650 660 LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD PLGDTASNLG 670 680 690 700 710 720 SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ KPSIQKADGT ATAPPPRSNH 730 740 750 760 770 780 AAEEASSEDE EEEEVQAMQS FNSTQQNETE PNQQVVGTEE RIPIPLMDYI LNVMKFVESI 790 800 810 820 830 840 LSNNTTDDHC QEFVNQKGLL PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV 850 860 870 880 890 900 LQEGLLQLDS ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH 910 920 930 940 950 960 AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV LLSLCTPNSL 970 980 990 1000 1010 1020 PSGCEFGQAD MQKLVPKDEK ADGEQDGAAG SMDASTQGLL EGIGLDGDTL APMETDEPTA 1030 1040 1050 1060 1070 1080 SDSKGKSKIT PAMAARIKQI KPLLSASSRL GRALAELFGL LVKLCVGSPV RQRRSHHAAS 1090 1100 1110 1120 1130 1140 TTTAPTPAAR STASALTKLL TKGLSWQPPP YTPTPRFRLT FFICSVGFTS PMLFDERKYP 1150 1160 1170 1180 1190 1200 YHLMLQKFLC SGGHNALFET FNWALSMGGK VPVSEGLEHS DLPDGTGEFL DAWLMLVEKM 1210 1220 1230 1240 1250 1260 VNPTTVLESP HSLPAKLPGG VQNFPQFSAL RFLVVTQKAA FTCIKNLWNR KPLKVYGGRM 1270 1280 1290 1300 1310 1320 AESMLAILCH ILRGEPVIRE RLSKEKEGSR GEEDTGQEEG GSRREPQVNQ QQLQQLMDMG 1330 1340 1350 1360 1370 1380 FTREHAMEAL LNTSTMEQAT EYLLTHPPPI MGGVVRDLSM SEEDQMMRAI AMSLGQDIPM 1390 1400 1410 1420 1430 1440 DQRAESPEEV ACRKEEEERK AREKQEEEEA KCLEKFQDAD PLEQDELHTF TDTMLPGCFH 1450 1460 1470 1480 1490 1500 LLDELPDTVY RVCDLIMTAI KRNGADYRDM ILKQVVNQVW EAADVLIKAA LPLTTSDTKT 1510 1520 1530 1540 1550 1560 VSEWISQMAT LPQASNLATR ILLLTLLFEE LKLPCAWVVE SSGILNVLIK LLEVVQPCLQ 1570 1580 1590 1600 1610 1620 AAKEQKEVQT PKWITPVLLL IDFYEKTAIS SKRRAQMTKY LQSNSNNWRW FDDRSGRWCS 1630 1640 1650 1660 1670 1680 YSASNNSTID SAWKSGETSV RFTAGRRRYT VQFTTMVQVN EETGNRRPVM LTLLRVPRLN 1690 1700 1710 1720 1730 1740 KNSKNSNGQE LEKTLEESKE MDIKRKENKG NDTPLALEST NTEKETSLEE TKIGEILIQG 1750 1760 1770 1780 1790 1800 LTEDMVTVLI RACVSMLGVP VDPDTLHATL RLCLRLTRDH KYAMMFAELK STRMILNLTQ 1810 1820 1830 1840 1850 1860 SSGFNGFTPL VTLLLRHIIE DPCTLRHTME KVVRSAATSG AGSTTSGVVS GSLGSREINY 1870 1880 1890 1900 1910 1920 ILRVLGPAAC RNPDIFTEVA NCCIRIALPA PRGSGTASDD EFENLRIKGP NAVQLVKTTP 1930 1940 1950 1960 1970 1980 LKPSPLPVIP DTIKEVIYDM LNALAAYHAP EEADKSDPKP GVMTQEVGQL LQDMGDDVYQ 1990 2000 2010 2020 2030 2040 QYRSLTRQSS DFDTQSGFSI NSQVFAADGA STETSASGTS QGEASTPEES RDGKKDKEGD 2050 2060 2070 2080 2090 2100 RASEEGKQKG KGSKPLMPTS TILRLLAELV RSYVGIATLI ANYSYTVGQS ELIKEDCSVL 2110 2120 2130 2140 2150 2160 AFVLDHLLPH TQNAEDKDTP ALARLFLASL AAAGSGTDAQ VALVNEVKAA LGRALAMAES 2170 2180 2190 2200 2210 2220 TEKHARLQAV MCIISTIMES CPSTSSFYSS ATAKTQHNGM NNIIRLFLKK GLVNDLARVP 2230 2240 2250 2260 2270 2280 HSLDLSSPNM ANTVNAALKP LETLSRIVNQ PSSLFGSKSA SSKNKSEQDA QGASQDSSSN 2290 2300 2310 2320 2330 2340 QQDPGEPGEA EVQEEDHDVT QTEVADGDIM DGEAETDSVV IAGQPEVLSS QEMQVENELE 2350 2360 2370 2380 2390 2400 DLIDELLERD GGSGNSTIIV SRSGEDESQE DVLMDEAPSN LSQASTLQAN REDSMNILDP 2410 2420 2430 2440 2450 2460 EDEEEHTQEE DSSGSNEDED DSQDEEEEEE EDEEDDQEDD EGEEGDEDDD DDGSEMELDE 2470 2480 2490 2500 2510 2520 DYPDMNASPL VRFERFDRED DLIIEFDNMF SSATDIPPSP GNIPTTHPLM VRHADHSSLT 2530 2540 2550 2560 2570 2580 LGSGSSTTRL TQGIGRSQRT LRQLTANTGH TIHVHYPGNR QPNPPLILQR LLGPSAAADI 2590 2600 2610 2620 2630 2640 LQLSSSLPLQ SRGRARLLVG NDDVHIIARS DDELLDDFFH DQSTATSQAG TLSSIPTALT 2650 2660 2670 2680 2690 2700 RWTEECKVLD AESMHDCVSV VKVSIVNHLE FLRDEELEER REKRRKQLAE EETKITDKGK 2710 2720 2730 2740 2750 2760 EDKENRDQSA QCTASKSNDS TEQNLSDGTP MPDSYPTTPS STDAATSESK ETLGTLQSSQ 2770 2780 2790 2800 2810 2820 QQPTLPTPPA LGEVPQELQS PAGEGGSSTQ LLMPVEPEEL GPTRPSGEAE TTQMELSPAP 2830 2840 2850 2860 2870 2880 TITSLSPERA EDSDALTAVS SQLEGSPMDT SSLASCTLEE AVGDTSAAGS SEQPRAGSST 2890 2900 2910 2920 2930 2940 PGDAPPAVAE VQGRSDGSGE SAQPPEDSSP PASSESSSTR DSAVAISGAD SRGILEEPLP 2950 2960 2970 2980 2990 3000 STSSEEEDPL AGISLPEGVD PSFLAALPDD IRREVLQNQL GIRPPTRTAP STNSSAPAVV 3010 3020 3030 3040 3050 3060 GNPGVTEVSP EFLAALPPAI QEEVLAQQRA EQQRRELAQN ASSDTPMDPV TFIQTLPSDL 3070 3080 3090 3100 3110 3120 RRSVLEDMED SVLAVMPPDI AAEAQALRRE QEARQRQLMH ERLFGHSSTS ALSAILRSPA 3130 3140 3150 3160 3170 3180 FTSRLSGNRG VQYTRLAVQR GGTFQMGGSS SHNRPSGSNV DTLLRLRGRL LLDHEALSCL 3190 3200 3210 3220 3230 3240 LVLLFVDEPK LNTSRLHRVL RNLCYHAQTR HWVIRSLLSI LQRSSESELC IETPKLTTSE 3250 3260 3270 3280 3290 3300 EKGKKSSKSC GSSSHENRPL DLLHKMESKS SNQLSWLSVS MDAALGCRTN IFQIQRSGGR 3310 3320 3330 3340 3350 3360 KHTEKHASGG STVHIHPQAA PVVCRHVLDT LIQLAKVFPS HFTQQRTKET NCESDRERGN 3370 3380 3390 3400 3410 3420 KACSPCSSQS SSSGICTDFW DLLVKLDNMN VSRKGKNSVK SVPVSAGGEG ETSPYSLEAS 3430 3440 3450 3460 3470 3480 PLGQLMNMLS HPVIRRSSLL TEKLLRLLSL ISIALPENKV SEAQANSGSG ASSTTTATST 3490 3500 3510 3520 3530 3540 TSTTTTTAAS TTPTPPTAPT PVTSAPALVA ATAISTIVVA ASTTVTTPTT ATTTVSISPT 3550 3560 3570 3580 3590 3600 TKGSKSPAKV SDGGSSSTDF KMVSSGLTEN QLQLSVEVLT SHSCSEEGLE DAANVLLQLS 3610 3620 3630 3640 3650 3660 RGDSGTRDTV LKLLLNGARH LGYTLCKQIG TLLAELREYN LEQQRRAQCE TLSPDGLPEE 3670 3680 3690 3700 3710 3720 QPQTTKLKGK MQSRFDMAEN VVIVASQKRP LGGRELQLPS MSMLTSKTST QKFFLRVLQV 3730 3740 3750 3760 3770 3780 IIQLRDDTRR ANKKAKQTGR LGSSGLGSAS SIQAAVRQLE AEADAIIQMV REGQRARRQQ 3790 3800 3810 3820 3830 3840 QAATSESSQS EASVRREESP MDVDQPSPSA QDTQSIASDG TPQGEKEKEE RPPELPLLSE 3850 3860 3870 3880 3890 3900 QLSLDELWDM LGECLKELEE SHDQHAVLVL QPAVEAFFLV HATERESKPP VRDTRESQLA 3910 3920 3930 3940 3950 3960 HIKDEPPPLS PAPLTPATPS SLDPFFSREP SSMHISSSLP PDTQKFLRFA ETHRTVLNQI 3970 3980 3990 4000 4010 4020 LRQSTTHLAD GPFAVLVDYI RVLDFDVKRK YFRQELERLD EGLRKEDMAV HVRRDHVFED 4030 4040 4050 4060 4070 4080 SYRELHRKSP EEMKNRLYIV FEGEEGQDAG GLLREWYMII SREMFNPMYA LFRTSPGDRV 4090 4100 4110 4120 4130 4140 TYTINPSSHC NPNHLSYFKF VGRIVAKAVY DNRLLECYFT RSFYKHILGK SVRYTDMESE 4150 4160 4170 4180 4190 4200 DYHFYQGLVY LLENDVSTLG YDLTFSTEVQ EFGVCEVRDL KPNGANILVT EENKKEYVHL 4210 4220 4230 4240 4250 4260 VCQMRMTGAI RKQLAAFLEG FYEIIPKRLI SIFTEQELEL LISGLPTIDI DDLKSNTEYH 4270 4280 4290 4300 4310 4320 KYQSNSIQIQ WFWRALRSFD QADRAKFLQF VTGTSKVPLQ GFAALEGMNG IQKFQIHRDD 4330 4340 4350 4360 RSTDRLPSAH TCFNQLDLPA YESFEKLRHM LLLAIQECSE GFGLA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor." Chen D., Kon N., Li M., Zhang W., Qin J., Gu W. Cell 121:1071-1083(2005) [PubMed: 15989956] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH CDKN2A, MUTAGENESIS OF CYS-4341.
[2]	"Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis." Zhong Q., Gao W., Du F., Wang X. Cell 121:1085-1095(2005) [PubMed: 15989957] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF CYS-4341.
[3]	"Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histones." Liu Z., Oughtred R., Wing S.S. Mol. Cell. Biol. 25:2819-2831(2005) [PubMed: 15767685] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
[4]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Homo sapiens LASU1 (large structure of UREB1) mRNA, complete cds." Miyazaki K., Okamoto Y., Sakamoto M., Kato C., Ozaki T., Watanabe K., Nakagawara A. Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 959-4374 (ISOFORM 3). Tissue: Brain.
[6]	"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed: 9205841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1166-4374 (ISOFORM 2). Tissue: Brain.
[7]	"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O. DNA Res. 7:273-281(2000) [PubMed: 10997877] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1246-2418. Tissue: Brain.
[8]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2451-4374. Tissue: Umbilical cord blood.
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3953-4374. Tissue: Ovary and Placenta.
[10]	Kim J.W., Lee Y., Hong Y.M., Hong M., Choe I.S. Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4029-4374.
[11]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4067-4374.
[12]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4320-4374. Tissue: Melanoma.
[13]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1395; SER-1907 AND SER-2362, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"Over-expression of human UREB1 in colorectal cancer: HECT domain of human UREB1 inhibits the activity of tumor suppressor p53 protein." Yoon S.Y., Lee Y., Kim J.H., Chung A.-S., Joo J.H., Kim C.-N., Kim N.-S., Choe I.S., Kim J.W. Biochem. Biophys. Res. Commun. 326:7-17(2005) [PubMed: 15567145] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF TYR-4268 AND CYS-4341.
[15]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1907; SER-2362; SER-3808; SER-3816; SER-3919; THR-3924 AND THR-3927, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1395; SER-1907; SER-2362; SER-2887 AND SER-2918, MASS SPECTROMETRY. Tissue: Epithelium.
[17]	"Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage." Hall J.R., Kow E., Nevis K.R., Lu C.K., Luce K.S., Zhong Q., Cook J.G. Mol. Biol. Cell 18:3340-3350(2007) [PubMed: 17567951] [Abstract] Cited for: FUNCTION, INTERACTION WITH CDC6.
[18]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2377; SER-3797; SER-3816 AND THR-3822, MASS SPECTROMETRY.
[19]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1907, MASS SPECTROMETRY.
[20]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1907, MASS SPECTROMETRY. Tissue: Platelet.
[21]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1084 AND SER-2526, MASS SPECTROMETRY.
[22]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1907 AND SER-2362, MASS SPECTROMETRY.
[23]	"The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein." Zhao X., Heng J.I.-T., Guardavaccaro D., Jiang R., Pagano M., Guillemot F., Iavarone A., Lasorella A. Nat. Cell Biol. 10:643-653(2008) [PubMed: 18488021] [Abstract] Cited for: FUNCTION, INTERACTION WITH MYCN, MUTAGENESIS OF CYS-4341.
[24]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1368; SER-1395; SER-1907; SER-2362; SER-2365; SER-2887; SER-3662; SER-3919; THR-3924 AND THR-3927, MASS SPECTROMETRY.
[25]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-509; LYS-1840 AND LYS-2248, MASS SPECTROMETRY.
[26]	"Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation." Froyen G., Corbett M., Vandewalle J., Jarvela I., Lawrence O., Meldrum C., Bauters M., Govaerts K., Vandeleur L., Van Esch H., Chelly J., Sanlaville D., van Bokhoven H., Ropers H.-H., Laumonnier F., Ranieri E., Schwartz C.E., Abidi F. , Tarpey P.S., Futreal P.A., Whibley A., Raymond F.L., Stratton M.R., Fryns J.-P., Scott R., Peippo M., Sipponen M., Partington M., Mowat D., Field M., Hackett A., Marynen P., Turner G., Gecz J. Am. J. Hum. Genet. 82:432-443(2008) [PubMed: 18252223] [Abstract] Cited for: VARIANTS MRXS-TURNER HIS-2981; TRP-4013 AND CYS-4187, INVOLVEMENT IN MRX17.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AY772009 mRNA. Translation: AAV90838.1.
DQ097177 mRNA. Translation: AAY98258.1.
AY929612 mRNA. Translation: AAX24125.1.
AL592046, Z94044, Z97054 Genomic DNA. Translation: CAI39580.1.
Z94044, AL592046, Z97054 Genomic DNA. Translation: CAI42354.1.
Z97054, AL592046, Z94044 Genomic DNA. Translation: CAI42654.1.
AB071605 mRNA. Translation: BAC06833.1. Frameshift.
AB002310 mRNA. Translation: BAA20771.2.
AB046798 mRNA. Translation: BAB13404.1. Sequence problems.
AF161390 mRNA. Translation: AAF28950.1. Frameshift.
BC002602 mRNA. Translation: AAH02602.2.
BC063505 mRNA. Translation: AAH63505.1.
AF057569 mRNA. Translation: AAC62492.1. Different initiation.
CR456813 mRNA. Translation: CAG33094.1.
AL162050 mRNA. Translation: CAB82393.1.

IPI

IPI00445401.
IPI00456919.
IPI00643153.

PIR

T47165.

RefSeq

NP_113584.3.

UniGene

Hs.136905

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EKK	NMR	-	A	1317-1356	[»]
3G1N	X-ray	2.60	A/B	4005-4374	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q7Z6Z7. 7 interactions.

STRING

Q7Z6Z7.

PTM databases

PhosphoSite

Q7Z6Z7.

Proteomic databases

PRIDE

Q7Z6Z7.

Genome annotation databases

Ensembl

ENST00000218328; ENSP00000218328; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000262854; ENSP00000262854; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000276009; ENSP00000276009; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000342160; ENSP00000340648; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000375220; ENSP00000364368; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000396323; ENSP00000379615; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000424562; ENSP00000415122; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000426907; ENSP00000403236; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000427052; ENSP00000401253; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000432528; ENSP00000409234; ENSG00000086758; Homo sapiens. [Genome view]
ENST00000446750; ENSP00000413651; ENSG00000086758; Homo sapiens. [Genome view]

GeneID

10075.

KEGG

hsa:10075.

UCSC

uc004dso.1. human.

Organism-specific databases

CTD

10075.

GeneCards

GC0XM053575.

HGNC

HGNC:30892. HUWE1.

HPA

CAB022718.
HPA002548.

MIM

300697. gene.
300705. phenotype.
300706. phenotype.

PharmGKB

PA128394567.

HUGE

Search...
Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q7Z6Z7.

Gene expression databases

ArrayExpress

Q7Z6Z7.

Bgee

Q7Z6Z7.

Genevestigator

Q7Z6Z7.

GermOnline

ENSG00000086758. Homo sapiens.

Family and domain databases

InterPro

IPR010309. E3_ubiquit_lig_DUF908.
IPR010314. E3_ubiquit_lig_DUF913.
IPR000569. HECT.
IPR000449. UBA/transl_elong_EF1B_N.
IPR015940. UBA/transl_elong_EF1B_N_euk.
IPR004170. WWE-dom.
[Graphical view]

Pfam

PF06012. DUF908. 1 hit.
PF06025. DUF913. 1 hit.
PF00632. HECT. 1 hit.
PF00627. UBA. 1 hit.
PF02825. WWE. 1 hit.
[Graphical view]

SMART

SM00119. HECTc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]

PROSITE

PS50237. HECT. 1 hit.
PS50030. UBA. 1 hit.
PS50330. UIM. False negative.
PS50918. WWE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

38085.

SOURCE

Search...

Entry information

Entry name

HUWE1_HUMAN

Accession

Primary (citable) accession number: Q7Z6Z7
Secondary accession number(s): O15029 , Q4G2Z2, Q5H961, Q6P4D0, Q8NG67, Q9BUI0, Q9HCJ4, Q9NSL6, Q9P0A9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	August 30, 2005
Last modified:	November 3, 2009
This is version 75 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.