O94874 (UFL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 UFM1-protein ligase 1
EC=6.3.2.-

Alternative name(s):
LZAP-binding protein

Gene names

Name:	UFL1
Synonyms:	KIAA0776, NLBP

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	794 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 UFM1-protein ligase that mediates ufmylation of target proteins such as DDRGK1/C20orf116. The function of ufmylation is unknown. May act as a tumor suppressor by inhibiting cell invasion, blocking NF-kappa-B signaling and increasing stability of CDK5RAP3. Ref.9 Ref.10
Subunit structure	Interacts with DDRGK1/C20orf116 and UFC1. Interacts with CDK5RAP3. Interacts with RELA. Ref.9 Ref.10
Subcellular location	Endoplasmic reticulum. Cytoplasm. Note: In cytoplasm colocalizes with CDK5RAP3. Ref.9 Ref.10
Tissue specificity	Ubiquitously expressed, with a high expression in liver (at protein level). Low expression in several invasive hepatocellular carcinomas, such HepG2, Hep3B, HLE and PLC. Ref.9
Post-translational modification	Ubiquitinated, leading to its degradation by the proteasome. Interaction with CDK5RAP3 protects each other against ubiquitination and degradation via the proteasome. Ref.10
Sequence similarities	Belongs to the UFL1 family.
Sequence caution	The sequence AAH15377.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence. The sequence BAA34496.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
Molecular function	Ligase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.10. Source: UniProtKB negative regulation of protein ubiquitination Inferred from direct assay Ref.10. Source: UniProtKB protein ufmylation Inferred from direct assay Ref.9. Source: UniProtKB
Cellular component	endoplasmic reticulum Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular function	UFM1 conjugating enzyme activity Inferred from direct assay Ref.9. Source: UniProtKB protein binding Inferred from physical interaction Ref.9Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASP4	P49662	1	EBI-1048088,EBI-1057327
CDK5RAP3	Q96JB5	1	EBI-1048088,EBI-718818

Alternative products

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

Isoform 1 (identifier: O94874-1)

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 2 (identifier: O94874-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: O94874-3)

The sequence of this isoform differs from the canonical sequence as follows:
     508-509: PL → QV
     510-794: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 794	794	E3 UFM1-protein ligase 1		PRO_0000050771
Regions
	Region	1 – 212	212	Required for E3 UFM1-protein ligase activity
	Region	121 – 250	130	Involved in CDK5RAP3-binding
Amino acid modifications
	Modified residue	458	1	Phosphoserine Ref.6 Ref.7
	Modified residue	571	1	N6-acetyllysine Ref.8
Natural variations
	Alternative sequence	1 – 65	65	Missing in isoform 2.		VSP_038759
	Alternative sequence	508 – 509	2	PL → QV in isoform 3.		VSP_038760
	Alternative sequence	510 – 794	285	Missing in isoform 3.		VSP_038761
	Natural variant	137	1	V → F. Corresponds to variant rs28372909 [ dbSNP | Ensembl ].		VAR_034037

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 21, 2005. Version 2. Checksum: C6C1777455551991	FASTA	794	89,595
	10 20 30 40 50 60 MADAWEEIRR LAADFQRAQF AEATQRLSER NCIEIVNKLI AQKQLEVVHT LDGKEYITPA 70 80 90 100 110 120 QISKEMRDEL HVRGGRVNIV DLQQVINVDL IHIENRIGDI IKSEKHVQLV LGQLIDENYL 130 140 150 160 170 180 DRLAEEVNDK LQESGQVTIS ELCKTYDLPG NFLTQALTQR LGRIISGHID LDNRGVIFTE 190 200 210 220 230 240 AFVARHKARI RGLFSAITRP TAVNSLISKY GFQEQLLYSV LEELVNSGRL RGTVVGGRQD 250 260 270 280 290 300 KAVFVPDIYS RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VSYIKKRYKT TQLLFLKAAC 310 320 330 340 350 360 VGQGLVDQVE ASVEEAISSG TWVDIAPLLP TSLSVEDAAI LLQQVMRAFS KQASTVVFSD 370 380 390 400 410 420 TVVVSEKFIN DCTELFRELM HQKAEKEMKN NPVHLITEED LKQISTLESV STSKKDKKDE 430 440 450 460 470 480 RRRKATEGSG SMRGGGGGNA REYKIKKVKK KGRKDDDSDD ESQSSHTGKK KPEISFMFQD 490 500 510 520 530 540 EIEDFLRKHI QDAPEEFISE LAEYLIKPLN KTYLEVVRSV FMSSTTSASG TGRKRTIKDL 550 560 570 580 590 600 QEEVSNLYNN IRLFEKGMKF FADDTQAALT KHLLKSVCTD ITNLIFNFLA SDLMMAVDDP 610 620 630 640 650 660 AAITSEIRKK ILSKLSEETK VALTKLHNSL NEKSIEDFIS CLDSAAEACD IMVKRGDKKR 670 680 690 700 710 720 ERQILFQHRQ ALAEQLKVTE DPALILHLTS VLLFQFSTHS MLHAPGRCVP QIIAFLNSKI 730 740 750 760 770 780 PEDQHALLVK YQGLVVKQLV SQSKKTGQGD YPLNNELDKE QEDVASTTRK ELQELSSSIK 790 DLVLKSRKSS VTEE
	Isoform 2 [UniParc]. Checksum: CC168D0709E0D82A	FASTA	729	82,098
	10 20 30 40 50 60 MRDELHVRGG RVNIVDLQQV INVDLIHIEN RIGDIIKSEK HVQLVLGQLI DENYLDRLAE 70 80 90 100 110 120 EVNDKLQESG QVTISELCKT YDLPGNFLTQ ALTQRLGRII SGHIDLDNRG VIFTEAFVAR 130 140 150 160 170 180 HKARIRGLFS AITRPTAVNS LISKYGFQEQ LLYSVLEELV NSGRLRGTVV GGRQDKAVFV 190 200 210 220 230 240 PDIYSRTQST WVDSFFRQNG YLEFDALSRL GIPDAVSYIK KRYKTTQLLF LKAACVGQGL 250 260 270 280 290 300 VDQVEASVEE AISSGTWVDI APLLPTSLSV EDAAILLQQV MRAFSKQAST VVFSDTVVVS 310 320 330 340 350 360 EKFINDCTEL FRELMHQKAE KEMKNNPVHL ITEEDLKQIS TLESVSTSKK DKKDERRRKA 370 380 390 400 410 420 TEGSGSMRGG GGGNAREYKI KKVKKKGRKD DDSDDESQSS HTGKKKPEIS FMFQDEIEDF 430 440 450 460 470 480 LRKHIQDAPE EFISELAEYL IKPLNKTYLE VVRSVFMSST TSASGTGRKR TIKDLQEEVS 490 500 510 520 530 540 NLYNNIRLFE KGMKFFADDT QAALTKHLLK SVCTDITNLI FNFLASDLMM AVDDPAAITS 550 560 570 580 590 600 EIRKKILSKL SEETKVALTK LHNSLNEKSI EDFISCLDSA AEACDIMVKR GDKKRERQIL 610 620 630 640 650 660 FQHRQALAEQ LKVTEDPALI LHLTSVLLFQ FSTHSMLHAP GRCVPQIIAF LNSKIPEDQH 670 680 690 700 710 720 ALLVKYQGLV VKQLVSQSKK TGQGDYPLNN ELDKEQEDVA STTRKELQEL SSSIKDLVLK SRKSSVTEE
	Isoform 3 [UniParc]. Checksum: 84F3FC58B6D8F072	FASTA	509	57,583
	10 20 30 40 50 60 MADAWEEIRR LAADFQRAQF AEATQRLSER NCIEIVNKLI AQKQLEVVHT LDGKEYITPA 70 80 90 100 110 120 QISKEMRDEL HVRGGRVNIV DLQQVINVDL IHIENRIGDI IKSEKHVQLV LGQLIDENYL 130 140 150 160 170 180 DRLAEEVNDK LQESGQVTIS ELCKTYDLPG NFLTQALTQR LGRIISGHID LDNRGVIFTE 190 200 210 220 230 240 AFVARHKARI RGLFSAITRP TAVNSLISKY GFQEQLLYSV LEELVNSGRL RGTVVGGRQD 250 260 270 280 290 300 KAVFVPDIYS RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VSYIKKRYKT TQLLFLKAAC 310 320 330 340 350 360 VGQGLVDQVE ASVEEAISSG TWVDIAPLLP TSLSVEDAAI LLQQVMRAFS KQASTVVFSD 370 380 390 400 410 420 TVVVSEKFIN DCTELFRELM HQKAEKEMKN NPVHLITEED LKQISTLESV STSKKDKKDE 430 440 450 460 470 480 RRRKATEGSG SMRGGGGGNA REYKIKKVKK KGRKDDDSDD ESQSSHTGKK KPEISFMFQD 490 500 EIEDFLRKHI QDAPEEFISE LAEYLIKQV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:277-286(1998) [PubMed: 9872452] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Substantia nigra.
[3]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORMS 1 AND 3). Tissue: Kidney and Testis.
[6]	"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-458, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, MASS SPECTROMETRY. Tissue: Liver.
[8]	"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-571, MASS SPECTROMETRY.
[9]	"A novel type of E3 ligase for the Ufm1 conjugation system." Tatsumi K., Sou Y.S., Tada N., Nakamura E., Iemura S., Natsume T., Kang S.H., Chung C.H., Kasahara M., Kominami E., Yamamoto M., Tanaka K., Komatsu M. J. Biol. Chem. 285:5417-5427(2010) [PubMed: 20018847] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH DDRGK1 AND UFC1.
[10]	"A novel LZAP-binding protein, NLBP, inhibits cell invasion." Kwon J., Cho H.J., Han S.H., No J.G., Kwon J.Y., Kim H. J. Biol. Chem. 285:12232-12240(2010) [PubMed: 20164180] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDK5RAP3; DDRGK1 AND RELA.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB018319 mRNA. Translation: BAA34496.1. Different initiation. AK295934 mRNA. Translation: BAG58719.1. AL590404, AL132776 Genomic DNA. Translation: CAH73710.1. AL132776, AL590404 Genomic DNA. Translation: CAI20401.1. CH471051 Genomic DNA. Translation: EAW48507.1. BC015377 mRNA. Translation: AAH15377.1. Sequence problems. BC028608 mRNA. Translation: AAH28608.1. BC036379 mRNA. Translation: AAH36379.1.
IPI	IPI00844000. IPI00955456. IPI00955462.
RefSeq	NP_056138.1. NM_015323.4.
UniGene	Hs.149367.
3D structure databases
ProteinModelPortal	O94874.
ModBase	Search...
Protein-protein interaction databases
IntAct	O94874. 8 interactions.
STRING	O94874.
PTM databases
PhosphoSite	O94874.
Proteomic databases
PeptideAtlas	O94874.
PRIDE	O94874.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000369278; ENSP00000358283; ENSG00000014123.
GeneID	23376.
KEGG	hsa:23376.
UCSC	uc003por.1. human.
Organism-specific databases
CTD	23376.
GeneCards	GC06P096969.
HGNC	HGNC:23039. UFL1.
HPA	HPA030558. HPA030559. HPA030560.
MIM	613372. gene.
neXtProt	NX_O94874.
PharmGKB	PA134937763.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000002112.
HOGENOM	HBG445146.
HOVERGEN	HBG060009.
InParanoid	O94874.
OMA	RIINGHI.
OrthoDB	EOG4N30NG.
PhylomeDB	O94874.
Gene expression databases
ArrayExpress	O94874.
Bgee	O94874.
CleanEx	HS_KIAA0776.
Genevestigator	O94874.
GermOnline	ENSG00000014123. Homo sapiens.
Family and domain databases
InterPro	IPR018611. E3_UFM1_ligase_1. [Graphical view]
Pfam	PF09743. DUF2042. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	45462.
SOURCE	Search...

Entry information

Entry name

UFL1_HUMAN

Accession

Primary (citable) accession number: O94874
Secondary accession number(s): A0PJ53 , B4DJ57, C0H5X5, Q8N765, Q9NTQ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 21, 2005
Last sequence update:	June 21, 2005
Last modified:	January 25, 2012
This is version 79 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.