Reviewed, UniProtKB/Swiss-Prot Q14511 (CASL_HUMAN)

Names and origin

Protein names

Recommended name:
    Enhancer of filamentation 1
      Short name=hEF1
Alternative name(s):
    CRK-associated substrate-related protein
      Short name=CAS-L
      Short name=CasL
    p105
    Neural precursor cell expressed developmentally down-regulated protein 9
      Short name=NEDD-9
    Cas scaffolding protein family member 2
    Renal carcinoma antigen NY-REN-12
Cleaved into the following chain:
    1- Recommended name:
            Enhancer of filamentation 1 p55

Gene names

Name:	NEDD9
Synonyms:	CASL, CASS2

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

General annotation (Comments)

Function	Docking protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. May function in transmitting growth control signals between focal adhesions at the cell periphery and the mitotic spindle in response to adhesion or growth factor signals initiating cell proliferation. May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRK, NCK and SHPTP2 to the tyrosine phosphorylated form.
Subunit structure	Interacts with BCAR3 and SH2D3C By similarity. Homodimer. Can heterodimerize with HLH proteins ID2, E12, E47 and also with p130cas. Forms complexes in vivo with related adhesion focal tyrosine kinase (RAFTK), adapter protein CRKL and LYN kinase. Interacts with MICAL and TXNL4/DIM1.
Subcellular location	Cytoplasm › cell cortex. Nucleus. Golgi apparatus. Cell projection › lamellipodium. Cytoplasm. Cell junction › focal adhesion. Note= Localizes to both the cell nucleus and the cell periphery and is differently localized in fibroblasts and epithelial cells. In fibroblasts is predominantly nuclear and in some cells is present in the Golgi apparatus. In epithelial cells localized predominantly in the cell periphery with particular concentration in lamellipodia but is also found in the nucleus. Isoforms p105 and p115 are predominantly cytoplasmic and associate with focal adhesions while p55 associates with mitotic spindle. Enhancer of filamentation 1 p55: Spindle. Cytoplasm › cytoskeleton.
Tissue specificity	Widely expressed. Higher levels detected in kidney, lung, and placenta. Also detected in T-cells, B-cells and diverse cell lines. The protein has been detected in lymphocytes, in diverse cell lines, and in lung tissues.
Induction	Activated upon induction of cell growth.
Domain	Contains a central domain containing multiple potential SH2-binding sites and a C-terminal domain containing a divergent helix-loop-helix (HLH) motif. The SH2-binding sites putatively bind CRK, NCK and ABL SH2 domains. The HLH motif confers specific interaction with the HLH proteins ID2, E12 and E47. It is absolutely required for the induction of pseudohyphal growth in yeast and mediates homodimerization and heterodimerization with p130cas. The SH3 domain interacts with two proline-rich regions of focal adhesion kinase.
Post-translational modification	Cell cycle-regulated processing produces four isoforms: p115, p105, p65, and p55. Isoform p115 arises from p105 phosphorylation and appears later in the cell cycle. Isoform p55 arises from p105 as a result of cleavage at a caspase cleavage-related site and it appears specifically at mitosis. The p65 isoform is poorly detected. Focal adhesion kinase 1 phosphorylates the protein at the YDYVHL motif (conserved among all cas proteins). The SRC family kinases (FYN, SRC, LCK and CRK) are recruited to the phosphorylated sites and can phosphorylate other tyrosine residues. Ligation of either integrin beta-1 or B-cell antigen receptor on tonsillar B-cells and B-cell lines promotes tyrosine phosphorylation and both integrin and BCR-mediated tyrosine phosphorylation requires an intact actin network. In fibroblasts transformation with oncogene v-ABL results in an increase in tyrosine phosphorylation. Transiently phosphorylated following CD3 cross-linking and this phosphorylated form binds to CRK and C3G. A mutant lacking the SH3 domain is phosphorylated upon CD3 cross-linking but not upon integrin beta-1 cross-linking. Tyrosine phosphorylation occurs upon stimulation of the G-protein coupled C1a calcitonin receptor in rabbit. Calcitonin-stimulated tyrosine phosphorylation is mediated by calcium- and protein kinase C-dependent mechanisms and requires the integrity of the actin cytoskeleton.
Involvement in disease	May play a role in pathways leading to progression of cancer.
Sequence similarities	Belongs to the CAS family. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Cell adhesion Cell cycle Cell division Growth regulation Mitosis
Cellular component	Cell junction Cell projection Cytoplasm Cytoskeleton Golgi apparatus Nucleus
Coding sequence diversity	Polymorphism
Domain	SH3 domain
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	actin filament bundle formation Ref.14 Non-traceable author statement. Source: UniProtKB cell adhesion Ref.8 Non-traceable author statement. Source: ProtInc cell division Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton organization Ref.14 Non-traceable author statement. Source: UniProtKB integrin-mediated signaling pathway Ref.14 Non-traceable author statement. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW regulation of cell growth Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-KW cell junction Inferred from electronic annotation. Source: UniProtKB-KW cell projection Inferred from electronic annotation. Source: UniProtKB-KW nucleus Ref.1 Traceable author statement. Source: ProtInc spindle Ref.8 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.14 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 834	834	Enhancer of filamentation 1		PRO_0000089328
	Chain	1 – ?		Enhancer of filamentation 1 p55		PRO_0000296242
Regions
	Domain	3 – 65	63	SH3
	Region	102 – 229	128	Interacts strongly with spindle-regulatory protein D1M1
	Region	710 – 760	51	Divergent helix-loop-helix motif
	Motif	360 – 363	4	Caspase cleavage related site
Amino acid modifications
	Modified residue	12	1	Phosphotyrosine
	Modified residue	92	1	Phosphotyrosine By similarity
	Modified residue	166	1	Phosphotyrosine
	Modified residue	177	1	Phosphotyrosine By similarity
	Modified residue	189	1	Phosphotyrosine By similarity
	Modified residue	317	1	Phosphotyrosine
	Modified residue	345	1	Phosphotyrosine
Natural variations
	Natural variant	577	1	T → M: dbSNP rs3734401.		VAR_021857

Sequences

	Sequence		Length	Mass (Da)
	Q14511-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: C54DEC36C8C8E9E6	FASTA	834	92,861
	10 20 30 40 50 60 MKYKNLMARA LYDNVPECAE ELAFRKGDIL TVIEQNTGGL EGWWLCSLHG RQGIVPGNRV 70 80 90 100 110 120 KLLIGPMQET ASSHEQPASG LMQQTFGQQK LYQVPNPQAA PRDTIYQVPP SYQNQGIYQV 130 140 150 160 170 180 PTGHGTQEQE VYQVPPSVQR SIGGTSGPHV GKKVITPVRT GHGYVYEYPS RYQKDVYDIP 190 200 210 220 230 240 PSHTTQGVYD IPPSSAKGPV FSVPVGEIKP QGVYDIPPTK GVYAIPPSAC RDEAGLREKD 250 260 270 280 290 300 YDFPPPMRQA GRPDLRPEGV YDIPPTCTKP AGKDLHVKYN CDIPGAAEPV ARRHQSLSPN 310 320 330 340 350 360 HPPPQLGQSV GSQNDAYDVP RGVQFLEPPA ETSEKANPQE RDGVYDVPLH NPPDAKGSRD 370 380 390 400 410 420 LVDGINRLSF SSTGSTRSNM STSSTSSKES SLSASPAQDK RLFLDPDTAI ERLQRLQQAL 430 440 450 460 470 480 EMGVSSLMAL VTTDWRCYGY MERHINEIRT AVDKVELFLK EYLHFVKGAV ANAACLPELI 490 500 510 520 530 540 LHNKMKRELQ RVEDSHQILS QTSHDLNECS WSLNILAINK PQNKCDDLDR FVMVAKTVPD 550 560 570 580 590 600 DAKQLTTTIN TNAEALFRPG PGSLHLKNGP ESIMNSTEYP HGGSQGQLLH PGDHKAQAHN 610 620 630 640 650 660 KALPPGLSKE QAPDCSSSDG SERSWMDDYD YVHLQGKEEF ERQQKELLEK ENIMKQNKMQ 670 680 690 700 710 720 LEHHQLSQFQ LLEQEITKPV ENDISKWKPS QSLPTTNSGV SAQDRQLLCF YYDQCETHFI 730 740 750 760 770 780 SLLNAIDALF SCVSSAQPPR IFVAHSKFVI LSAHKLVFIG DTLTRQVTAQ DIRNKVMNSS 790 800 810 820 830 NQLCEQLKTI VMATKMAALH YPSTTALQEM VHQVTDLSRN AQLFKRSLLE MATF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human enhancer of filamentation 1, a novel p130cas-like docking protein, associates with focal adhesion kinase and induces pseudohyphal growth in Saccharomyces cerevisiae." Law S.F., Estojak J., Wang B., Mysliwiec T., Kruh G., Golemis E.A. Mol. Cell. Biol. 16:3327-3337(1996) [PubMed: 8668148] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Structure and function of Cas-L, a 105-kD Crk-associated substrate-related protein that is involved in beta 1 integrin-mediated signaling in lymphocytes." Minegishi M., Tachibana K., Sato T., Iwata S., Nojima Y., Morimoto C. J. Exp. Med. 184:1365-1375(1996) [PubMed: 8879209] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymphoma.
[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 (JUL-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]. Tissue: Brain.
[6]	"Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells." Manie S.N., Beck A.R.P., Astier A., Law S.F., Canty T., Hirai H., Druker B.J., Avraham H., Haghayeghi N., Sattler M., Salgia R., Griffin J.D., Golemis E.A., Freedman A.S. J. Biol. Chem. 272:4230-4236(1997) [PubMed: 9020138] [Abstract] Cited for: INCREASED TYROSINE PHOSPHORYLATION BY LIGATION OF INTEGRIN-B1 AND BCR.
[7]	"Tyrosine phosphorylation of Crk-associated substrates by focal adhesion kinase. A putative mechanism for the integrin-mediated tyrosine phosphorylation of Crk-associated substrates." Tachibana K., Urano T., Fujita H., Ohashi Y., Kamiguchi K., Iwata S., Hirai H., Morimoto C. J. Biol. Chem. 272:29083-29090(1997) [PubMed: 9360983] [Abstract] Cited for: PHOSPHORYLATION AT TYROSINE RESIDUES BY FOCAL ADHESION KINASE.
[8]	"Cell cycle-regulated processing of HEF1 to multiple protein forms differentially targeted to multiple subcellular compartments." Law S.F., Zhang Y.-Z., Klein-Szanto A.J.P., Golemis E.A. Mol. Cell. Biol. 18:3540-3551(1998) [PubMed: 9584194] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[9]	"T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G." Ohashi Y., Tachibana K., Kamiguchi K., Fujita H., Morimoto C. J. Biol. Chem. 273:6446-6451(1998) [PubMed: 9497377] [Abstract] Cited for: PHOSPHORYLATION AT TYROSINE RESIDUES UPON CD3 CROSS-LINKING.
[10]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[11]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed: 12522270] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-166, MASS SPECTROMETRY.
[12]	"Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain." Law S.F., Zhang Y.-Z., Fashena S.J., Toby G., Estojak J., Golemis E.A. Exp. Cell Res. 252:224-235(1999) [PubMed: 10502414] [Abstract] Cited for: CHARACTERIZATION OF CARBOXY-TERMINAL DOMAIN.
[13]	"Evidence that Dim1 associates with proteins involved in pre-mRNA splicing, and delineation of residues essential for Dim1 interactions with hnRNP F and Npw38/PQBP-1." Zhang Y.-Z., Lindblom T., Chang A., Sudol M., Sluder A.E., Golemis E.A. Gene 257:33-43(2000) [PubMed: 11054566] [Abstract] Cited for: INTERACTION WITH TXNL4.
[14]	"MICAL, a novel CasL interacting molecule, associates with vimentin." Suzuki T., Nakamoto T., Ogawa S., Seo S., Matsumura T., Tachibana K., Morimoto C., Hirai H. J. Biol. Chem. 277:14933-14941(2002) [PubMed: 11827972] [Abstract] Cited for: INTERACTION WITH MICAL.
[15]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-12, MASS SPECTROMETRY. Tissue: T-cell.
[16]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-317 AND TYR-345, MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L43821 mRNA. Translation: AAA98770.1. U64317 mRNA. Translation: AAB53696.1. AL136139, AL139807 Genomic DNA. Translation: CAI22676.1. AL139807, AL136139 Genomic DNA. Translation: CAI21579.1. CH471087 Genomic DNA. Translation: EAW55301.1. BC040207 mRNA. Translation: AAH40207.1.
RefSeq	NP_006394.1.
UniGene	Hs.699288
3D structure databases
HSSP	HSSP built from PDB template 1JQQ based on UniProtKB P80667.
SMR	Q14511. Positions 5-65.
ModBase	Search...
PTM databases
PhosphoSite	Q14511.
Genome annotation databases
Ensembl	ENSG00000111859. Homo sapiens. [Contig view]
GeneID	4739.
KEGG	hsa:4739.
Organism-specific databases
H-InvDB	HIX0025044.
HGNC	HGNC:7733. NEDD9.
MIM	602265. gene.
PharmGKB	PA31538.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q14511.
HOVERGEN	Q14511.
Gene expression databases
ArrayExpress	Q14511.
CleanEx	HS_NEDD9.
GermOnline	ENSG00000111859. Homo sapiens.
Family and domain databases
InterPro	IPR014928. Serine_rich. IPR001452. SH3. [Graphical view]
Pfam	PF08824. Serine_rich. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00452. SH3DOMAIN.
ProDom	PD000066. SH3. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00326. SH3. 1 hit. [Graphical view]
PROSITE	PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	18276.
SOURCE	Search...

Entry information

Entry name

CASL_HUMAN

Accession

Primary (citable) accession number: Q14511
Secondary accession number(s): Q5T9R4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)