Reviewed, UniProtKB/Swiss-Prot Q9HCE7 (SMUF1_HUMAN)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase SMURF1
      Short name=hSMURF1
    EC=6.3.2.-
Alternative name(s):
    SMAD ubiquitination regulatory factor 1
    SMAD-specific E3 ubiquitin-protein ligase 1

Gene names

Name:	SMURF1
Synonyms:	KIAA1625

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	757 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 accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with receptor-regulated SMADs specific for the BMP pathway, SMAD1 and SMAD5, in order to trigger their ubiquitination and degradation and hence their inactivation.
Pathway	Protein modification; protein ubiquitination.
Sequence similarities	Contains 1 C2 domain. Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. Contains 2 WW domains.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Molecular function	Ligase
Gene Ontology (GO)
Biological process	BMP signaling pathway Inferred from Experiment. Source: Reactome cell differentiation Ref.3 Inferred from direct assay. Source: UniProtKB ectoderm development Ref.3 Traceable author statement. Source: UniProtKB negative regulation of BMP signaling pathway Ref.3 Traceable author statement. Source: UniProtKB positive regulation of protein ubiquitination Inferred from direct assay. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from direct assay. Source: UniProtKB protein export from nucleus Inferred from direct assay. Source: UniProtKB protein ubiquitination during ubiquitin-dependent protein catabolic process Ref.3 Inferred from direct assay. Source: UniProtKB ubiquitin-dependent SMAD protein catabolic process Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	I-SMAD binding Inferred from physical interaction. Source: UniProtKB R-SMAD binding Inferred from physical interaction. Source: UniProtKB activin binding Inferred from physical interaction. Source: UniProtKB ubiquitin-protein ligase activity Ref.3 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RUNX2	Q13950	1	EBI-976466,EBI-976402

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q9HCE7-1)

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 Short (identifier: Q9HCE7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     269-294: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 757	757	E3 ubiquitin-protein ligase SMURF1		PRO_0000120326
Regions
	Domain	1 – 99	99	C2
	Domain	234 – 267	34	WW 1
	Domain	306 – 339	34	WW 2
	Domain	420 – 757	338	HECT
Sites
	Active site	725	1	Glycyl thioester intermediate
Natural variations
	Alternative sequence	269 – 294	26	Missing in isoform Short.		VSP_006812
	Natural variant	466	1	S → Y: dbSNP rs13246077.		VAR_052959
Experimental info
	Mutagenesis	725	1	C → A: Loss of ubiquitination capacity.

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified December 13, 2001. Version 2. Checksum: 89A171CFC47B40E9	FASTA	757	86,114
	10 20 30 40 50 60 MSNPGTRRNG SSIKIRLTVL CAKNLAKKDF FRLPDPFAKI VVDGSGQCHS TDTVKNTLDP 70 80 90 100 110 120 KWNQHYDLYV GKTDSITISV WNHKKIHKKQ GAGFLGCVRL LSNAISRLKD TGYQRLDLCK 130 140 150 160 170 180 LNPSDTDAVR GQIVVSLQTR DRIGTGGSVV DCRGLLENEG TVYEDSGPGR PLSCFMEEPA 190 200 210 220 230 240 PYTDSTGAAA GGGNCRFVES PSQDQRLQAQ RLRNPDVRGS LQTPQNRPHG HQSPELPEGY 250 260 270 280 290 300 EQRTTVQGQV YFLHTQTGVS TWHDPRIPSP SGTIPGGDAA FLYEFLLQGH TSEPRDLNSV 310 320 330 340 350 360 NCDELGPLPP GWEVRSTVSG RIYFVDHNNR TTQFTDPRLH HIMNHQCQLK EPSQPLPLPS 370 380 390 400 410 420 EGSLEDEELP AQRYERDLVQ KLKVLRHELS LQQPQAGHCR IEVSREEIFE ESYRQIMKMR 430 440 450 460 470 480 PKDLKKRLMV KFRGEEGLDY GGVAREWLYL LCHEMLNPYY GLFQYSTDNI YMLQINPDSS 490 500 510 520 530 540 INPDHLSYFH FVGRIMGLAV FHGHYINGGF TVPFYKQLLG KPIQLSDLES VDPELHKSLV 550 560 570 580 590 600 WILENDITPV LDHTFCVEHN AFGRILQHEL KPNGRNVPVT EENKKEYVRL YVNWRFMRGI 610 620 630 640 650 660 EAQFLALQKG FNELIPQHLL KPFDQKELEL IIGGLDKIDL NDWKSNTRLK HCVADSNIVR 670 680 690 700 710 720 WFWQAVETFD EERRARLLQF VTGSTRVPLQ GFKALQGSTG AAGPRLFTIH LIDANTDNLP 730 740 750 KAHTCFNRID IPPYESYEKL YEKLLTAVEE TCGFAVE
	Isoform Short. Checksum: F106E00CA3C210AA	FASTA	731	83,440
	10 20 30 40 50 60 MSNPGTRRNG SSIKIRLTVL CAKNLAKKDF FRLPDPFAKI VVDGSGQCHS TDTVKNTLDP 70 80 90 100 110 120 KWNQHYDLYV GKTDSITISV WNHKKIHKKQ GAGFLGCVRL LSNAISRLKD TGYQRLDLCK 130 140 150 160 170 180 LNPSDTDAVR GQIVVSLQTR DRIGTGGSVV DCRGLLENEG TVYEDSGPGR PLSCFMEEPA 190 200 210 220 230 240 PYTDSTGAAA GGGNCRFVES PSQDQRLQAQ RLRNPDVRGS LQTPQNRPHG HQSPELPEGY 250 260 270 280 290 300 EQRTTVQGQV YFLHTQTGVS TWHDPRIPRD LNSVNCDELG PLPPGWEVRS TVSGRIYFVD 310 320 330 340 350 360 HNNRTTQFTD PRLHHIMNHQ CQLKEPSQPL PLPSEGSLED EELPAQRYER DLVQKLKVLR 370 380 390 400 410 420 HELSLQQPQA GHCRIEVSRE EIFEESYRQI MKMRPKDLKK RLMVKFRGEE GLDYGGVARE 430 440 450 460 470 480 WLYLLCHEML NPYYGLFQYS TDNIYMLQIN PDSSINPDHL SYFHFVGRIM GLAVFHGHYI 490 500 510 520 530 540 NGGFTVPFYK QLLGKPIQLS DLESVDPELH KSLVWILEND ITPVLDHTFC VEHNAFGRIL 550 560 570 580 590 600 QHELKPNGRN VPVTEENKKE YVRLYVNWRF MRGIEAQFLA LQKGFNELIP QHLLKPFDQK 610 620 630 640 650 660 ELELIIGGLD KIDLNDWKSN TRLKHCVADS NIVRWFWQAV ETFDEERRAR LLQFVTGSTR 670 680 690 700 710 720 VPLQGFKALQ GSTGAAGPRL FTIHLIDANT DNLPKAHTCF NRIDIPPYES YEKLYEKLLT 730 AVEETCGFAV E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM LONG). Tissue: Brain.
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation." Zhu H., Kavsak P., Abdollah S., Wrana J.L., Thomsen G.H. Nature 400:687-693(1999) [PubMed: 10458166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-731 (ISOFORM SHORT).
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB046845 mRNA. Translation: BAB13451.1. Different initiation. AC004893 Genomic DNA. Translation: AAC62434.1. AC073468 Genomic DNA. No translation available. AC114500 Genomic DNA. No translation available. AF199364 mRNA. Translation: AAF08298.2.
IPI	IPI00217054. IPI00219332.
RefSeq	NP_065162.1. NP_851994.1.
UniGene	Hs.189329
3D structure databases
HSSP	HSSP built from PDB template 1K9R based on UniProtKB P46937.
SMR	Q9HCE7. Positions 375-750.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HCE7. 1 interaction.
PTM databases
PhosphoSite	Q9HCE7.
Proteomic databases
PRIDE	Q9HCE7.
Genome annotation databases
Ensembl	ENSG00000198742. Homo sapiens. [Contig view]
GeneID	57154.
KEGG	hsa:57154.
NMPDR	fig|9606.3.peg.29036.
Organism-specific databases
GeneCards	GC07M098463.
H-InvDB	HIX0006884.
HGNC	HGNC:16807. SMURF1.
MIM	605568. gene.
PharmGKB	PA134987175.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9HCE7.
HOVERGEN	Q9HCE7.
Enzyme and pathway databases
Pathway_Interaction_DB	bmppathway. BMP receptor signaling. hdac_classi_pathway. Signaling events mediated by HDAC Class I. tgfbrpathway. TGF-beta receptor signaling.
Reactome	REACT_12034. Signaling by BMP. REACT_6844. Signaling by TGF beta.
Gene expression databases
ArrayExpress	Q9HCE7.
Bgee	Q9HCE7.
CleanEx	HS_SMURF1.
GermOnline	ENSG00000198742. Homo sapiens.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR018029. C2_membr_targeting. IPR000569. HECT. IPR001202. WW_Rsp5_WWP. [Graphical view]
Pfam	PF00168. C2. 1 hit. PF00632. HECT. 1 hit. PF00397. WW. 2 hits. [Graphical view]
SMART	SM00239. C2. 1 hit. SM00119. HECTc. 1 hit. SM00456. WW. 2 hits. [Graphical view]
PROSITE	PS50004. C2. 1 hit. PS50237. HECT. 1 hit. PS01159. WW_DOMAIN_1. 1 hit. PS50020. WW_DOMAIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	63133.
SOURCE	Search...

Entry information

Entry name

SMUF1_HUMAN

Accession

Primary (citable) accession number: Q9HCE7
Secondary accession number(s): O75853, Q9UJT8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 13, 2001
Last sequence update:	December 13, 2001
Last modified:	June 16, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)